Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy.

Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with the use of anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately account for variable individual susceptibility. This suggests the presence of other determinants. In this case series, we describe 2 women with breast cancer who developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women. To our knowledge, this is the 1st report of an association between truncating TTN variants and CCMP. Because truncations in TTN are the most common cause of familial and sporadic dilated cardiomyopathy, further research is needed to establish their prevalence in patients presenting with CCMP.

Factors associated with the high tuberculosis case rate in an urban area.

SETTING: The Rotterdam region, the Netherlands, 1995-2006. OBJECTIVE: To identify factors associated with the high tuberculosis (TB) case rate in an urban area. DESIGN: Municipalities were divided into urban and semi-urban/rural municipalities. We compared the characteristics of TB cases and stratified case rates according to age group, immigrant status and place and time of infection between the two areas. RESULTS: The TB case rate in urban municipalities was 3.8-fold higher than in semi-urban/rural municipalities. After stratification for country of birth, the rate ratios were lower (1.7 for immigrants and 2.8 for non-immigrants). Immigrants had most frequently acquired their infection abroad (47% of urban and 62% of semi-urban/rural immigrant cases). In 40% of urban cases and 27% of semi-urban/rural cases, the infection was recently acquired in the Netherlands, translating into a 5.7-fold higher recent transmission case rate for the urban population. CONCLUSIONS: The high urban TB case rate was related to the high proportion of urban immigrants who frequently reactivated an infection acquired abroad. Recent transmission also contributed to a substantial part of the TB caseload in urban municipalities among both urban immigrants and non-immigrants. The authors propose a package of targeted interventions to address the identified factors associated with the high urban TB case rate.

Transmission classification model to determine place and time of infection of tuberculosis cases in an urban area.

We conducted a population-based study in the Rotterdam region of The Netherlands to determine the place and time of infection of tuberculosis (TB) cases using conventional epidemiological and genotyping information. In particular, we focused on the extent of misclassification if genotyping was not combined with epidemiological information. Cases were divided into those with a unique mycobacterial DNA fingerprint, a clustering fingerprint, and an unknown fingerprint. We developed transmission classification trees for each category to determine whether patients were infected in a foreign country or recently (2 years) infected in The Netherlands. Of all TB cases during the 12-year study period, 38% were infected in a foreign country, 36% resulted from recent transmission in The Netherlands, and 18% resulted from remote infection in The Netherlands, while in the remaining cases (9%) either the time or place of infection could not be determined. The conventional epidemiological data suggested that at least 29% of clustered cases were not part of recent chains of transmission. Cases with unknown fingerprints, almost all culture negative, relatively frequently had confirmed epidemiological links with a recent pulmonary TB case in The Netherlands and were more often identified by contact tracing. Our findings highlight the idea that genotyping should be combined with conventional epidemiological investigation to establish the place and time of infection of TB cases as accurately as possible. A standardized way of classifying TB into recently, remotely, and foreign-acquired disease provides indicators for surveillance and TB control program performance that can be used to decide on interventions and allocation of resources.

Multifocal spasm with acetylcholine in Prinzmetal angina.

A 60-year-old female patient with Prinzmetal angina and a single non-critical (<50%) focal obstruction in the right coronary artery was referred for percutaneous coronary intervention. Coronary angiography with provocative testing using incremental doses of acetylcholine demonstrated diffuse mild vasoconstriction and multifocal hyperreactive vasoconstriction in apparently normal coronary segments but not at the site of the nonsignificant obstruction. We refrained from intervention and advised avoidance of beta-blockade, and continuation of medical therapy with nitrates and calcium antagonists. (Neth Heart J 2008;16:134-6.).

[Congenital long QT-syndrome: the cause of recurrent syncope and sudden death at a young age]. / Congenitaal lange-QT-tijdsyndroom: oorzaak van recidiverende wegrakingen en plotse dood op jonge leeftijd.

Congenital long QT-syndrome (LQTS) was diagnosed in three patients. The first patient, a 10-year-old girl, presented with recurrent episodes of syncope during swimming and was diagnosed with type 1 LQTS. The second patient, a 36-year-old asymptomatic man, was accidentally diagnosed with type 2 LQTS. His family history revealed syncope and sudden death at a young age after auditory stimuli. Type 3 LQTS was diagnosed post-mortem in a 16-year-old boy who died during his sleep. All clinical diagnoses were confirmed by genetic testing. Congenital LQTS is one of the leading causes of sudden cardiac death at a young age. Mutations in genes encoding for myocardial ion channel proteins lead to a prolonged QT-interval and abnormal ST-T segments in the 12-lead ECG. Patients may present with syncope or sudden cardiac death caused by ventricular tachyarrhythmias. Genotype-specific differences in ECG-abnormalities and triggers for cardiac events may help to distinguish the type of LQTS and make possible the initiation of genotype-specific treatment before the results of genetic testing are known. Identification of the genetic substrate by genetic testing, genotype-specific treatment, and the possibility of treatment with an implantable cardioverter-defibrillator have all led to dramatic improvement in the prognosis of patients with LQTS. Therefore, young patients with unexplained recurrent syncope after specific stimuli and those with atypical forms of epilepsy should be referred for cardiologic evaluation in a specialised centre.

Completeness of notification of tuberculosis in The Netherlands: how reliable is record-linkage and capture-recapture analysis?

The aim of this study was to describe a systematic process of record-linkage, cross-validation, case-ascertainment and capture-recapture analysis to assess the quality of tuberculosis registers and to estimate the completeness of notification of incident tuberculosis cases in The Netherlands in 1998. After record-linkage and cross-validation 1499 tuberculosis patients were identified, of whom 1298 were notified, resulting in an observed under-notification of 13.4%. After adjustment for possible imperfect record-linkage and remaining false-positive hospital cases observed under-notification was 7.3%. Log-linear capture-recapture analysis initially estimated a total number of 2053 (95% CI 1871-2443) tuberculosis cases, resulting in an estimated under-notification of 36.8%. After adjustment for possible imperfect record-linkage and remaining false-positive hospital cases various capture-recapture models estimated under-notification at 13.6%. One of the reasons for the higher than expected estimated under-notification in a country with a well-organized system of tuberculosis control might be that some tuberculosis cases, e.g. extrapulmonary tuberculosis, are managed by clinicians less familiar with notification of infectious diseases. This study demonstrates the possible impact of violation of assumptions underlying capture-recapture analysis, especially the perfect record-linkage, perfect positive predictive value and absent three-way interaction assumptions.

Not just any ICD device in patients with long-QT syndrome.

Patients with LQT syndrome are prone to lifethreatening arrhythmias. After surviving such an event, implantation of an ICD is indicated. There are, however, special subtle demands in the treatment of these patients. In this case report we describe our findings in a patient with LQT1 syndrome, and the pitfalls that can and must be avoided. (Neth Heart J 2007;15:418-21.).

[Delay in the diagnosis of tuberculosis]. / Vertraging bij de diagnostiek van tuberculose.

In five patients, a 46-year-old Surinamese man, a 45-year-old Dutch barkeeper, a 41-year-old woman from Eritrea, and an 18-year-old Afghan woman and her 43-year-old mother, tuberculosis was diagnosed and treated after a considerable delay. Such a late diagnosis and subsequent treatment is not uncommon for tuberculosis as the symptoms, physical examination, laboratory tests, imaging techniques and bacteriological results are often not very specific. However under certain circumstances, tuberculosis (including the extrapulmonary manifestations) should be considered at an earlier stage, especially among certain risk groups such as the homeless, drug addicts, immigrants and asylum seekers. In the five patients discussed the causes of delay were identified as: delay caused by the asymptomatic phase of the disease, the patient's delay in presenting, a delay on the part of the physician, a delay in diagnostic confirmation and a delay in the treatment.

Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery.

AIM: To assess the long-term cardioprotective effect of bisoprolol in a randomized high-risk population after successful major vascular surgery. High-risk patients were defined by the presence of one or more cardiac risk factor(s) and a dobutamine echocardiography test positive for ischaemia. METHODS: 1351 patients were screened prior to surgery, 846 patients had one or more risk factor(s), and 173 of these patients also had ischaemia during dobutamine echocardiography. One hundred and twelve patients could be randomized for additional bisoprolol therapy or standard care. Eleven patients died in the peri-operative period (up to 1 month after surgery). Randomized patients continued bisoprolol or standard care after surgery. During follow-up of 101 survivors (median 22 months, range 11-30) cardiac death or myocardial infarction was noted. No patient was lost during follow-up. Results The incidence of cardiac events during follow-up in the bisoprolol group was 12% vs 32% in the standard care group (P=0.025). Cardiac death occurred in 15 patients, nine patients in the standard care and in six in the bisoprolol group; myocardial infarction occurred in six patients, five in the standard care and one in the bisoprolol group. The odds ratio for cardiac death or myocardial infarction after surgery in high-risk patients with additional bisoprolol therapy was 0.30 (0.11-0.83). CONCLUSIONS: Bisoprolol significantly reduced long-term cardiac death and myocardial infarction in high-risk patients after successful major cardiac vascular surgery.

The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group.

BACKGROUND: Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery. METHODS: We performed a randomized, multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infarction within 30 days after major vascular surgery in patients at high risk for these events. High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography. Eligible patients were randomly assigned to receive standard perioperative care or standard care plus perioperative beta-blockade with bisoprolol. RESULTS: A total of 1351 patients were screened, and 846 were found to have one or more cardiac risk factors. Of these 846 patients, 173 had positive results on dobutamine echocardiography. Fifty-nine patients were randomly assigned to receive bisoprolol, and 53 to receive standard care. Fifty-three patients were excluded from randomization because they were already taking a beta-blocker, and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing. Two patients in the bisoprolol group died of cardiac causes (3.4 percent), as compared with nine patients in the standard-care group (17 percent, P=0.02). Nonfatal myocardial infarction occurred in nine patients given standard care only (17 percent) and in none of those given standard care plus bisoprolol (P<0.001). Thus, the primary study end point of death from cardiac causes or nonfatal myocardial infarction occurred in 2 patients in the bisoprolol group (3.4 percent) and 18 patients in the standard-care group (34 percent, P<0.001). CONCLUSIONS: Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction in high-risk patients who are undergoing major vascular surgery.

The social network characteristics of fibromyalgia patients compared with healthy controls.

OBJECTIVE: To assess structural social network characteristics and perceived loneliness in fibromyalgia syndrome (FMS) patients and healthy controls. METHODS: A cross-sectional, retrospective, case-control design was employed using a structured interview and a self-report questionnaire. We studied 25 female FMS patients and 25 matched healthy female controls. RESULTS: FMS patients had statistically significantly (P < 0.05) more intimate friends (mean 4.5) and more health care providers (mean 1.5) than did controls (2.3 and 0.0, respectively). The FMS patients more often initiated the contact with family members (mean 2.1) than did controls (mean 0.8). FMS patients did not perceive themselves as lonelier than controls perceived themselves. While there was a significant negative correlation between loneliness and social network variables among the controls, this relationship was not significant among the FMS patients. Among the patients, there was a strong correlation between the total social network size and the number of intimate friends, whereas in controls, the mean number of acquaintances was strongly correlated with the total network size. CONCLUSION: Compared to healthy controls, the social networks of FMS patients presented more linkages with intimate friends, family members, and health care providers. The lack of correlation between loneliness and social network variables for FMS patients is not what might be expected from social support theory. The assessment of structural social network characteristics along with social support variables may add to our understanding of the social functioning of FMS patients.

Social network characteristics in fibromyalgia or rheumatoid arthritis.

PURPOSE: To describe trends in the personal social network characteristics of the fibromyalgia patients compared with the network of patients with another chronic disorder such as rheumatoid arthritis (RA). METHODS: A structured interview was applied to 10 fibromyalgia patients and 10 matched RA patients. RESULTS: The networks of the 10 fibromyalgia and 10 RA patients were comparable in most respects, namely: the small number of intimate friends, the reliance for support on the spouse and the physician, and the relative lack of new social contacts. Furthermore, the fibromyalgia networks were closed networks within a small geographic area. These networks lacked initiative to establish and maintain relations, and can hardly fulfill the patients' psychosocial needs. CONCLUSION: Based on small numbers, the study provides some evidence that social networks of patients with fibromyalgia are more restricted than those of RA patients. Further studies should include larger numbers of patients to clarify cause and effect relationships and to suggest new directions in the treatment of chronic disorders such as fibromyalgia.

[Intravenous cholangiocholecystography using ioglycamide--indications and value]. / Intravenöse Cholangiocholezystographie mit Ioglykamid--Indikationen und Wertigkeit.

The introduction of modern methods of diagnostic imaging as sonography, CT and endoscopic retrograde cholangiopancreaticography has changed the value of intravenous cholegraphy. Since the introduction of the contrast medium Ioglycamide into clinical practice two years ago we evaluated the cholangiocholecystographies of 50 patients. The investigation was indicated, if no elucidation was achieved with sonography. Side effects were not registered with Ioglycamide. Indications and value of the method are discussed.

[Comparative ultrasound and computerized tomography studies of lumbar intervertebral disks and the lumbar canal]. / Ultraschall- und computertomographische Vergleichsuntersuchungen lumbaler Bandscheiben und des Lumbalkanals.

Sonography and computerised tomography were carried out on 61 lumbar segments (L5/S1, L4/5, L3/4) of 30 patients not having vertebrogenous symptoms. Transabdominal lumbar sonography with a 3.5 MHz sector probe proved to be a valuable imaging method, allowing to demonstrate the shape and dorsal outline of the lumbar discs. Bowl-shaped, right-angled and funnel-shaped configurations of the dorsal spinal canal are typical findings. The interpretation of the ultrasonic tomograms and the identification of normal anatomy are improved through comparative imaging by computerised tomography.

[Radiation dosage of premature infants caused by roentgen imaging of the thorax]. / Strahlenbelastung Frühgeborener durch Röntgenaufnahmen des Thorax.

The X-ray pictures of the thorax from premature infants must be prepared by conditions of neonatal intensive care. For this X-ray pictures are available very often single-puls generators only. The radiation exposure is dependent prominently on the type of the generator. The radiation exposure was compared between single-puls generators and 6-puls generators. The dosimetry was performed with CaF2-thermoluminescent dosimeters. The results of measurement demonstrated: In the radiation fields the radiation exposure is considerable higher by the single-puls generators than by the 6-puls generators. The indication to X-ray pictures of the thorax from premature infants under conditions of bed-side with single-puls generators must be very accuratly.

[Diagnostic strategy in primary malignant bone tumors in children]. / Zur Diagnosestrategie bei primären malignen Knochentumoren im Kindesalter.

Our experience concerning the diagnostic proceeding for primary malignant bone tumours in children and their often difficult differentiation from osteomyelitis are discussed. A retrospective evaluation of patient records of 66 children showed, that in 53 cases (41 with osteomyelitis, 12 malign tumours) diagnosis was immediately obtained from clinical and radiological results. For five more children osteomyelitis was proven by short term monitoring and paraclinical investigations, while in 8 cases final diagnosis required biopsy. CT was relevant for the evaluation of intraosseous and intramedullary extending tumours and mandatory for therapy planning. Conventional radiography, however, remains the most important method within the diagnostic strategy, but the need for close cooperation of radiologists and clinicians and a synoptic evaluation of clinical results, radiography and anamnestic data must be stressed.

[Diagnostic strategy in urolithiasis]. / Diagnosestrategie bei Urolithiasis.

The roentgenological diagnostics of urolithiasis must be carried out with regard to the therapeutic consequences. With the appropriate use of new imaging methods the prevailing techniques are native radiographs and sonography for proof or rejection of suspected renal calculus. Excretion urography is no longer justified as the primary method of investigation. Already practically proven diagnostic schedules are described. Interdisciplinary cooperation of radiologist and urologist is essential for the introduction of diagnostic strategies into practice.