Nintedanib for the treatment of symptomatic radiation pneumonitis. A Case Report.

Radiation induced pneumonitis is a common side effect of thoracic radiotherapy. We report a case of a patient diagnosed with symptomatic radiation pneumonitis and a serious contra-indication for corticosteroids. For that reason, the patient was treated with nintedanib instead. After several weeks of treatment her symptoms and chest CT improved significantly. This case shows that nintedanib might be an effective treatment of radiation pneumonitis if corticosteroids are contra-indicated.

[Why do patients discontinue their drugs?]. / Warum setzen Patienten eigenmächtig ärztlich verordnete Medikamente wieder ab?

BACKGROUND: Preventing or treating an illness just as avoiding its complications depend on the proper continuity of the intake of medication. Patients who discontinue their drugs unilaterally could call the resuIt of treatment into question. METHODS: Practising doctors who have the patients' trust asked, whether patients had discontinued their drugsandwhytheydidso. RESULTS: 250 patients from 19 doctors' offices admitted having discontinued, 54.8% of them because of adverse drug reactions, and 45.2% because of other reasons. Most of the adverse drug reactions were listed in the prescribing information, but there were also adverse events, which were not listet, and which could have a signal effect. Patients named a lot of different reasons for discontinuation not related to adverse drug reactions. The reasons were comprehensible and possibly could be avoided. CONCLUSION: Physicians should call attention to possible adverse events and should show up a benefit-risk profile. Reasons for discontinuation different from adverse drug reactions require physicians' efforts, but also help from family members, pharmacist, health insurance and health authority.

[Why do patients discontinue their drugs?]. / Warum setzen Patienten eigenmächtig ärztlich verordnete Medikamente wieder ab?

BACKGROUND: Preventing or treating an illness just as avoiding its complications depend on the proper continuity of the intake of medication. Patients who discontinue their drugs unilaterally could call the result of treatment into question. METHODS: Practising doctors who have the patients' trust asked, whether patients had discontinued their drugs and why they did so. RESULTS: 250 patients from 19 doctors' offices admitted having discontinued, 54.8% of them because of adverse drug reactions, and 45.2% because of other reasons. Most of the adverse drug reactions were listed in the prescribing information, but there were also adverse events, which were not listet, and which could have a signal effect. Patients named a lot of different reasons for discontinuation not related to adverse drug reactions. The reasons were comprehensible and possibly could be avoided. CONCLUSION: Physicians should call attention to possible adverse events and should show up a benefit-risk profile. Reasons for discontinuation different from adverse drug reactions require physicians' efforts, but also help from family members, pharmacist, health insurance and health authority.

[Do patients understand special terms in the product information?]. / Inwieweit verstehen Patienten Fachausdrücke in der Gebrauchsinformation? Pilotstudie: Patientenbefragung beim Arztbesuch in der Praxis.

The product of information for drugs is essential for the determinant use of drugs to guarantee the efficacy and safety of drugs. Supposition is the comprehension of special terms. The interviews of 277 patients by chance with 433 questionnaires (3313 questions) in the private practices showed that only a quarter of the special terms could be understood. Therefore it is necessary that the special terms must be translated to German or should be explained.

[Can cardiovascular diseases be reduced over 80% by a "superpill"? Review on the epidemiological study from Wald and Law, 2003]. / Können durch eine "Superpille" Herz-kreislauf-Krankheiten um über 8o% vermindert werden? Ubersicht über die epidemiologische Studie von Wald und Law aus dem Jahr 2003.

As a consequence of our "western" diet and lifestyle, the risk for cardiovascular diseases is increased in the western world. It can be decreased by influencing the LDL-cholesterol values, the blood pressure and the platelet aggregation. It is, however, not proven that lowering of serum homocysteine levels reduces the risk forcardiovascular diseases. Wald and Law suggest in their epidemiological study a polypill, which has as its ingredients a statin, an anti-hypertonic drug, folic acid, and aspirine. Overall, the risk reduction by a polypill is overestimated, since a threshold is currently not existing, in all drugs side effects and interactions are possible, pharmaceuticals are only labelled for specific indications, and with missing efficacy there could be a negative risk-benefit-relation. Indeed, a combined therapy with different drugs is in place in patients with higher risk and for secondary prevention, which is already risk-adjusted. The use of effective drugs, however, in patients without evidence of a positive risk-benefit-relation and without medical control cannot be justified. Therefore, the application of the polypill for subjects beyond 55 years of age is an illusion; by contrast, treatment of patients with a high risk for atherosclerotic diseases is already reality.

Pacing does not improve hypotension in patients with severe orthostatic hypotension--a prospective randomized cross-over pilot study.

BACKGROUND: Tachypacing has been suggested to compensate for drop in blood pressure as a technique to improve symptoms in patients with severe orthostatic hypotension secondary to autonomic dysfunction. To date, however, no randomized controlled studies have been performed to validate the approach. METHODS AND RESULTS: Six patients with severe orthostatic hypotension and chronotropic incompetence secondary to autonomic dysfunction underwent a prospective randomized cross-over tilt table study with no pacing and with temporary DDD pacing at 90 and 110 bpm. Time to syncope or pre-syncopal symptoms, blood pressure changes, stroke volume and cardiac output were recorded using real time hemodynamic monitoring and echocardiography. All patients, except for one, had a drop in blood pressure and syncope or pre-syncopal symptoms during tilt regardless of whether they were paced or not. There was also no difference in any of the measured hemodynamic and vasomotor parameters with pacing. CONCLUSIONS: Pacing did not produce any benefits in terms of symptoms or in any of the measured hemodynamic variables during tilt for patients with severe orthostatic hypotension secondary to autonomic dysfunction in this limited pilot study.

Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death.

OBJECTIVE: Characterization of a distinct, and as yet unexplained phenotype of sudden cardiac death (SCD). BACKGROUND: In a subgroup of patients with SCD, postmortem findings are limited to isolated idiopathic myocardial fibrosis (IMF). The absence of confounding factors may facilitate evaluation of the relationship between myocardial fibrosis and ventricular arrhythmogenesis. METHODS: Six patients with IMF were identified from a postmortem, consecutive 13-year series of 270 subjects presenting with SCD. Ventricular interstitial remodeling was assessed quantitatively and qualitatively and comparisons made with 6 age- and sex-matched control subjects who suffered noncardiac death. Myocardial collagen volume fraction and perivascular fibrosis ratio were determined and evidence for inflammatory response and apoptotic cell death was sought. The potential role of transforming growth factor beta 1 (TGF-beta(1)) in the pathogenesis of IMF was evaluated. RESULTS: Overall myocardial collagen volume fraction was 1.6-fold higher in IMF (mean age 34 +/- 4 yrs) vs. controls (mean age 34 +/- 4 yrs, .022 +/- .001 vs .013 +/- .001; P < .001). Collagen volume fraction increase was diffuse but disproportionately so in the LV inferior wall (3.4-fold increase; .035 +/- .005 vs .012 +/- .018; P < .001). Perivascular fibrosis ratio was also increased (.770 +/- .014 vs .723 +/- .010; P = .007). There was no evidence of either myocardial inflammatory response or myocyte apoptosis in cases or controls. Expression of TGF-beta(1) was significantly increased in IMF vs controls. CONCLUSION: IMF involves diffuse and heterogeneous remodeling of the ventricular interstitium, with a predilection for the LV inferior wall. TGF-beta(1) is a potential mediator of interstitial remodeling in IMF and SCD.

Familial atrial fibrillation is a genetically heterogeneous disorder.

OBJECTIVES: The aims of this study were to identify and characterize familial cases of atrial fibrillation (AF) in our clinical practice and to determine whether AF is genetically heterogeneous. BACKGROUND: Atrial fibrillation is not generally regarded as a heritable disorder, yet a genetic locus for familial AF was previously mapped to chromosome 10. METHODS: Of 2,610 patients seen in our arrhythmia clinic during an 18-month study period, 914 (35%) were diagnosed with AF. Familial cases were identified by history and medical records review. Four multi-generation families with autosomal dominant AF (FAF 1 to 4) were tested for linkage to the chromosome 10 AF locus. RESULTS: Fifty probands (5% of all AF patients; 15% of lone AF patients) were identified with lone AF (age 41 +/- 9 years) and a positive family history (1 to 9 additional relatives affected). In FAF 1 to 3, AF was associated with rapid ventricular response. In contrast, AF in FAF-4 was associated with a slow ventricular response and, with progression of the disease, junctional rhythm and cardiomyopathy. Genotyping of FAF 1 to 4 with deoxyribonucleic acid markers spanning the chromosome 10q22-q24 region excluded linkage of AF to this locus. In FAF-4, linkage was also excluded to the chromosome 3p22-p25 and lamin A/C loci associated with familial AF, conduction system disease, and dilated cardiomyopathy. CONCLUSIONS: Familial AF is more common than previously recognized, highlighting the importance of genetics in disease pathogenesis. In four families with AF, we have excluded linkage to chromosome 10q22-q24, establishing that at least two disease genes are responsible for this disorder.

[Diagnosing magnesium deficiency. Current recommendations of the Society for Magnesium Research]. / Diagnostikdes Magnesiummangels. Aktuelle Empfehlungen der Gesellschaft für Magnesium-forschung e. V.

The cardiovascular risk increases with decreasing serum levels of magnesium, and this already at concentrations within the previous reference range (0.70-1.10 mmol/L). For this reason, the Society for Magnesium Research has updated its 1986 recommendations for the diagnosis of magnesium deficiency. The diagnosis is based on the patient's history, his clinical symptoms, and the results of clinical-chemical investigations of plasma/serum and urine. Further diagnostic methods used include the determination of ionized serum magnesium and the magnesium retention test. The optimal serum magnesium concentration is > 0.80 mmol/L.

[Early hemodynamic cardiovascular reactions to nonionic low-osmolar contrast media in coronary angiography]. / Frühe hämodynamische kardiovaskuläre Reaktionen nichtionischer niederosmolarer Kontrastmittel bei der Koronarangiographie.

During the last 20 years there was an essential improvement in the tolerance of intravasal contrast media, leading to the nonionic low osmotic contrast media. In 26 consecutive patients with different stages of coronary heart disease the nonionic low osmolar contrast media iopamidol (Solutrast) and iopromide (Ultravist) were tested during coronary artery and left ventricular angiography. In both contrast media there were practically identically only slight early haemodynamic reactions with a decrease of heart rate, systolic pressure in the left ventricle, pressure in the aorta and an increase in pressure in the pulmonary artery and partly in cardiac output. These reactions are probably due to higher osmolality in comparison with blood. Therefore, further development of isotonic contrast media would be necessary.

[Acute and delayed aortocoronary bypass operations following transluminal angioplasty]. / Akute und verzögerte aortocornare Bypass-Operationen nach transluminaler Angioplastie.

Since 1980 348 PTCAs and 1288 CABs were performed at our institution (relation 1:4). In 15 cases (4.3%) emergency CAB was necessary because of complications encountered with PTCA. Two patients died, i.e. a mortality rate of 43.3% out of the emergency CABs or 0.6% out of the PTCA group; in 46.6% myocardial infarction occurred. In the same period 12 patients received CAB because of unsuccessful PTCA after a mean time of 4.6 months without increased operative morbidity. Interdisciplinary indication and experience, operation permanence and temporary coronary perfusion may decrease the complication rate.

[Early hemodynamic reactions of an ionic low osmolar and a nonionic contrast medium]. / Frühe hämodynamische kardiovaskuläre Rückwirkungen eines ionischen niederosmolaren und eines nichtionischen Kontrastmittels.

In eighty patients with different cardiac diseases the theoretically claimed reduced cardiovascular side effects in ionic and non-ionic low osmolar contrast media compared to those in conventional ionic and high-osmolar contrast media were tested during heart catheterization. The randomized application showed that there were only few reactions during left ventricle angiography and they did not differ between various ejections, while during selective coronary angiography in most cases heart rate and aortic pressures dropped significantly (p less than 0.05). These alterations were significantly (p less than 0.05) stronger in the conventional ionic and high-osmolar ioxitalamat (Telebrix 350) than in the ionic and non-ionic low-osmolar ioxaglat (Hexabrix) or non-ionic low-osmolar iopamidol (Solutrast 370).

Acute and chronic effects of the beta-receptor blocker mepindolol on hemodynamics and the portal circulation.

After administration of mepindolol, a reduction of the portal pressure was demonstrated in an acute study in six patients with varying degrees of cirrhosis of the liver and in a chronic study in 5 patients. The reduction of the portal pressure did not correlate very closely with the decrease in the cardiac output. It is therefore assumed that a beta 2-receptor effect with dilatation of the splanchnic vessels is the main mechanism. However, further studies are required to clarify the situation unequivocally. The properties of mepindolol (intrinsic sympathomimetic activity, slight negatively inotropic effect, non-selective action, primarily renal elimination) appear to be advantageous in this respect.