[Dyspnea in left-sided heart disease]. / Dyspnoe bei Linksherzerkrankungen.

Shortness of breath (dyspnea) is a common symptom in left-sided heart disease but clinically, patient symptoms show a high variability. Echocardiography is the mainstay for evaluating whether left-sided heart disease is the cause of dyspnea. If left-sided heart failure is diagnosed, this symptom complex must then be subjected to further etiological evaluation. Hypertensive, ischemic and valvular heart diseases are common, as well as atrial fibrillation. If the patient does not have angina pectoris, testing for ischemic heart disease should be done non-invasively by coronary computed tomography or testing for regional myocardial ischemia. Coronary revascularization is indicated only when a prognostically relevant ischemia of more than 10 % of the left ventricle is diagnosed. Diuretics are important for the relief of dyspnea but do not improve the prognosis of patients. In patients with reduced left ventricular function, combination therapy with angiotensin-converting enzyme (ACE) inhibitors, beta blockers and aldosterone antagonists improve the symptoms and prognosis. For treatment of heart failure with preserved ejection fraction evidence-based measures are still lacking. In this case the recommended therapy consists of optimal treatment of comorbidities, regulation of heart rate and blood pressure and participation in structured exercise programs. Angiotensin receptor blockers and aldosterone antagonists can be given in patients with more severe symptoms even though the available data are very sparse.

[Percutaneous coronary intervention versus bypass surgery in patients with diabetes and multivessel coronary disease. Coronary revascularization after FREEDOM]. / Perkutane koronare Intervention versus Bypass-Operation bei Patienten mit Diabetes und koronarer Mehrgefäßerkrankung. Koronarrevaskularisation nach FREEDOM.

Is coronary revascularization required in a patient with chronic stable coronary artery disease or can optimized medical therapy (OMT) alone be a sufficient alternative? This question has been controversially discussed for non-diabetics as well as for diabetics since the COURAGE and BARI 2D trials. According to our present knowledge, a patient will benefit from coronary revascularization only when either a non-invasive test method, such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) myocardial scintigraphy, stress echocardiography or stress nuclear magnetic resonance imaging, can detect relevant, objective evidence of ischemia >10% of the left ventricular myocardium or when a pathological fractional flow reserve (FFR) <0.80 can be measured in an invasive procedure for an angiographically detectable coronary stenosis. If similar relevant ischemia can be non-invasively or invasively objectified in a patient with chronic stable multivessel coronary artery disease, the often controversially discussed question arises particularly in diabetics whether a percutaneous coronary intervention (PCI) with implantation of drug-eluting stents or coronary artery bypass surgery should be favored. The FREEDOM study (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease), published in November 2012, was the first prospective randomized study to examine this issue in diabetic patients with multivessel coronary artery disease. Despite a higher rate of stroke in the surgical cohort, after an average follow-up time of 3.8 years a significant prognostic advantage in favor of bypass surgery was detected for a combined primary endpoint of all-cause mortality, nonfatal myocardial infarction and nonfatal stroke. Thus, in the new ESC guidelines on diabetes, pre-diabetes and cardiovascular diseases developed with the EASD of the European Society of Cardiology and published in 2013, coronary bypass surgery has a class I, level of evidence A recommendation for patients with diabetes mellitus, chronic stable multivessel coronary disease and a synergy between PCI with taxus and cardiac surgery (SYNTAX) score >22. The decision for or against a PCI/stent implantation or coronary bypass surgery in a diabetic patient with chronic stable multivessel coronary artery disease should therefore be made with the patient only after a detailed informed consent discussion and comprehensive explanation of both treatment options. In controversial cases, particularly with an equivocal SYNTAX score around 22, relevant comorbidities or anticipated method-specific complications, a one-stage ad hoc intervention during the diagnostic coronary angiography should be rejected in favor of a two-stage procedure with prior discussion of both treatment options in the heart team comprising noninvasive cardiologists, interventional cardiologists and cardiac surgeons.

[Prevalence of undetected diabetes mellitus in invasive and interventional cardiology. Silent diabetes in the catheterization laboratory]. / Prävalenz unentdeckter Glukosestoffwechselstörungen in der invasiven und interventionellen Kardiologie. "Silent diabetes" im Herzkatheterlabor.

In most randomized controlled trials on revascularization therapy for patients with ischemic coronary artery disease (CAD), the diabetes prevalence ranges between 15% and 35%. However, the true prevalence of diabetes is probably considerably underestimated in these trials. The European heart survey diabetes and the heart published in 2004 supplied strong evidence that there are many additional cases of undetected prediabetics and diabetics in any cardiology patient cohort. The long-term outcome of newly detected diabetics was found to be comparable to patients with already known diabetes mellitus. With this in mind, the Dresden silent diabetes study investigated the prevalence of undetected diabetes mellitus by oral glucose tolerance testing (OGTT) and comparative HbA1c sampling in 1,015 patients admitted for coronary angiography. Patients with known diabetes were excluded from the study.According to the OGTT only 513 patients (51%) were classified with normal glucose tolerance (NGT), 10 (1%) with isolated impaired fasting glucose (IFG), 349 (34%) with impaired glucose tolerance (IGT) and 143 (14%) were diagnosed with newly detected diabetes mellitus (DM). According to the HbA1c measurements 588 patients (58%) were classified as normal, 385 (38%) as borderline and only 42 (4%) were diagnosed with diabetes (DM). There was a significant correlation between the extent of CAD and glycemic status as defined by the OGTT. The number of patients with IGT and diabetes increased with the extent of CAD (IGT group p<0.001, diabetes group p=0.01). However, no such correlation was observed when glycemic status was defined by HbA1c testing.Based on these results an OGTT should be routinely performed in patients with known or suspected coronary artery disease undergoing coronary angiography for diagnosis of diabetes, as HbA1c measurements alone appear to miss a substantial proportion of patients. These findings are of high clinical relevance with regard to optimal coronary revascularization procedure chosen in catheterization laboratories, preferably drug-eluting stents in cases of diabetes mellitus or newly detected diabetes mellitus and preferably coronary bypass surgery in diabetics with multi-vessel disease and high SYNTAX scores.

Oral glucose tolerance test and HbA1c for diagnosis of diabetes in patients undergoing coronary angiography: [corrected] the Silent Diabetes Study.

AIMS/HYPOTHESIS: The primary aim of this study was to compare the results of HbA(1c) measurements with those of an OGTT for early diagnosis of 'silent diabetes' in patients with coronary artery disease (CAD) undergoing angiography without prediagnosed diabetes. A secondary aim was to investigate the correlation between the extent of CAD and the glycaemic status of the patient. METHODS: Data from 1,015 patients admitted for acute (n = 149) or elective (n = 866) coronary angiography were analysed. Patients with known diabetes were excluded from the study. Using the OGTT results, patients were classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. According to the results of the HbA(1c) measurements, patients were classified into three groups: normal (HbA(1c) <5.7% [<39 mmol/mol]), borderline (HbA(1c) 5.7-6.4% [39-47 mmol/mol]) and diabetes (HbA(1c) ≥6.5% [≥48 mmol/mol]). RESULTS: Based on the OGTT, 513 patients (51%) were classified with NGT, 10 (1%) with IFG, 349 (34%) with IGT and 149 (14%) were diagnosed with diabetes. According to HbA(1c) measurements, 588 patients (58%) were classified as normal, 385 (38%) as borderline and 42 (4%) were diagnosed with diabetes. The proportion of patients with IGT and diabetes increased with the extent of CAD (IGT ρ = 0.14, p < 0.001, diabetes ρ = 0.09, p = 0.01). No differences in HbA(1c) were seen among the groups with different extents of CAD (p = 0.652). CONCLUSIONS/INTERPRETATION: An OGTT should be performed routinely for diagnosis of diabetes in patients with CAD undergoing coronary angiography, since HbA(1c) measurement alone appears to miss a substantial proportion of patients with silent diabetes. A limitation of the study is that the OGTT was not performed before the angiography.

Detection of specific immunoglobulins (IgG, IgM, IgA, IgE) and total IgE levels in human trichinosis by means of the enzyme-linked immunosorbent assay (ELISA).

Sera from 58 cases of confirmed human trichinosis were examined over an 11-month period. The enzyme-linked immunosorbent assay (ELISA) was used for the detection of class-specific serum antibodies (IgG, IgM, IgA, IgE) and for total serum IgE. The indirect immunofluorescent test served as reference technique. The ELISA proved to be more sensitive. Specific IgG antibodies were detected by ELISA in 100% of the clinical cases. Both IgG and IgM were demonstrable throughout the observation period of 11 months. Specific serum IgA was seen in 62% of the patients during the first 3 months, presumably the result of stimulation of the immune system by the adult worms in the intestine. Specific serum IgE was seen in a few cases only at the onset of the disease. Total serum IgE levels were elevated in 32% of the patients in the first month of the disease and in 17% after 11 months, compared to 10% of healthy individuals.

Septal myectomy for left ventricular outflow tract obstruction after mitral valve repair.

We describe a patient with a left ventricular outflow tract obstruction after mitral valve repair. Intraoperative transesophageal echocardiography permitted us to recognize the role of a bulging septum in the development of a systolic motion of the mitral valve. A left ventricular septal myectomy and myotomy was able to relieve the left ventricular outflow tract obstruction and the systolic anterior motion of the mitral valve.

Valve repair for mitral regurgitation caused by isolated prolapse of the posterior leaflet.

BACKGROUND: Although prolapse of the posterior leaflet is the most common abnormality of the mitral valve causing dysfunction, the long-term results of mitral valve repair for this condition are seldom reported. METHODS: From October 1988 to June 1994, 208 patients (mean age, 59.4 years) with mitral regurgitation caused by isolated prolapse of the posterior leaflet underwent mitral valve repair alone or combined with myocardial revascularization (n = 30). The surgical techniques were quadrangular resection (n = 199) followed by annulus plication (n = 101) or sliding leaflet plasty (n = 98), use of artificial chordae (n = 5), or papillary muscle shortening (n = 4). All patients had an annuloplasty with a Carpentier ring. Mean follow-up was 3.4 +/- 0.1 years and total follow-up, 656 patient-years. RESULTS: There were six operative deaths (2.9%). Postoperative Doppler echocardiography found two cases of systolic anterior motion (1%), and echocardiographic studies at follow-up showed satisfactory mitral valve function in 97% of 112 patients. At 6 years, the actuarial survival rate was 87% +/- 7%, and freedom from thromboembolic complications, bleeding complications, and reoperation was 93% +/- 7%, 95% +/- 3%, and 95% +/- 4%, respectively. CONCLUSIONS: Mitral valve repair for regurgitation caused by prolapse of the posterior leaflet provides excellent survival at 6 years and should be considered the method of choice for its surgical treatment.

Fatal hepatotoxicity induced by hydralazine or labetalol.

Antihypertensive agents have been associated with adverse reactions that, if unrecognized by health practitioners, may have devastating consequences. The pattern of hepatotoxicity observed during therapy with the vasodilator hydralazine is highly variable, often making its diagnosis difficult. Serious hepatic injury induced by the alpha- and beta-adrenergic receptor antagonist labetalol has only recently been reported and therefore, many clinicians may be unaware of this adverse effect. Familiarity with the clinical features and course of hydralazine- and labetalol-induced hepatic injury is necessary to ensure prompt recognition and discontinuation of the agent.

Crossed-immunoelectrophoretic analyses of Trypanosoma cruzi epimastigote, metacyclic, and bloodstream forms.

Sonicated suspensions of epimastigote, metacyclic, or bloodstream forms of Trypanosoma cruzi were emulsified in Freund's complete adjuvant. Rabbits immunized with epimastigotes or metacyclics received five intramuscular (i.m.) injections of 1 x 10(9) sonicated trypanosomes at weekly intervals. Immunization with bloodstream forms included three i.m. injections of 5 x 10(7) and six injections of 2 x 10(8) sonicated trypanosomes. Selected antisera from these rabbits were employed in crossed immunoelectrophoretic studies against the homologous or heterologous extracts of sonicated trypanosomes. Extracts of epimastigote, metacyclic, and trypomastigotes produced 31, 29, and 11 precipitin peaks respectively against the homologous rabbit antisera. Tandem, crossed-immunoelectrophoresis of these extracts against antiepimastigote or antimetacyclic sera revealed that epimastigotes or metacyclics may each have at least four antigens that did not appear to be shared by the other, whereas each of these forms may have at least eight or nine antigens that were not detected with extracts from trypomastigotes. Cross-absorptions of antiepimastigote or antimetacyclic sera with live trypanosomes caused marked reductions in the numbers of precipitin peaks formed against the homologous extracts, but cross-absorptions with sonicated suspensions of epimastigotes or metacyclics showed that epimastigotes or metacyclics each have at least two antigens that were not detected in extracts of the other. Differentiation appeared to be accompanied by antigenic change. More antigens appear to be shared by epimastigotes and metacyclic forms than by trypomastigotes and epimastigotes or metacyclics.

Study on dosimetric parameters for stereotactic radiosurgery and intensity-modulated radiotherapy.

This study is an attempt to compare the dosimetric parameters of intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS) using patient data. Radiosurgery was delivered through circular tertiary collimators attached to a linear accelerator. Six patients who were treated with SRS were replanned and evaluated with the IMRT planning system. Contouring of all structures, including target volume, was done on the IMRT system to closely match the SRS system. Treatment plans were generated after specifying the goals in the prescription module. The NOMOS BEAK collimator attached to the NOMOS MIMiC delivery device was chosen for treatment delivery. Various parameters such as conformity index, homogeneity index, target volume coverage, nontarget tissue, and brainstem doses were calculated and compared between the IMRT and SRS systems. Patient data were divided into 2 groups based on the complexity of the lesion and the number of isocenters used for radiosurgery. Analysis was done for each group and for the cumulative data. Superior conformality and homogeneous dose distribution in IMRT for multiple isocenter cases were observed. In addition, critical structure volumes for 50%, 70%, and 90% of the prescribed dose were lower in IMRT compared to SRS treatment. However, nontarget tissue received significantly higher doses with IMRT plans. Results show that IMRT treatment modality produces similar results as radiosurgery for small, spherical lesions, whereas it is found to be superior to SRS for irregular lesions in terms of critical structure sparing and better dose homogeneity.

[Isolated prolapse of the posterior leaflet of the mitral valve. Results of reconstructive surgery]. / Prolapsus isolé du feuillet postérieur de la valve mitrale. Résultats de la chirurgie reconstructrice.

Out of 522 patients undergoing mitral valve reconstruction for mitral regurgitation between 1988 and June 1994, the authors studied 159 cases of isolated mitral regurgitation by prolapse of the posterior mitral leaflet. There were 98 men (62%) and 61 women (38%), with an average age of 58.4 +/- 10.4 years. The functional class and ejection fraction were 2.8 +/- 0.11 and 0.66 +/- 0.2 respectively. In 155 patients, surgery consisted in quadrangular resection of the prolapsed tissue, followed in 83 cases by sliding posterior valvuloplasty and in 72 cases by plicature of the annulus. In 4 cases, the prolapse was treated by implantation of artificial chordae tendinae. A Carpentier-Edwards ring was inserted in all cases. There were no hospital deaths. Echocardiography was performed before discharge from hospital and showed satisfactory mitral valve function in 98% of cases: slight systolic anterior motion (SAM) was observed in one case. All patients were followed up for an average of 3.67 +/- 0.10 years. At six years, survival was 93 +/- 7%; moreover, 93 +/- 7% and 97 +/- 3% of patients had no thromboembolic or haemorrhagic complications. Six patients were reoperated, three of them in the first year of follow-up. At six years, 95 +/- 5% of patients were free of reoperation and 81 +/- 11% were free of all complications. The authors conclude that the excellent medium term survival and the low rate of complications are evidence in favour of conservative surgery for treatment of mitral regurgitation due to prolapse of the posterior mitral leaflet.

The use of norfloxacin in a university hospital.

Because of increasing norfloxacin use and the development of resistant organisms, an evaluation was undertaken in a University Hospital to assess the appropriateness of norfloxacin for the treatment of urinary tract infections and to calculate the potential cost savings associated with more cost-effective antibiotic therapy. Medical records of 64 patients receiving norfloxacin for a 31-day period were concurrently reviewed. Of these, 58 patients were treated for urinary tract infections and four patients received urinary tract infection prophylaxis. Fourteen patients were prescribed solely empiric therapy whereas an additional 44 patients received definitive treatment confirmed by culture results. Based on the predetermined criteria, norfloxacin use for the definitive treatment of urinary tract infections was deemed to be appropriate in 34 of the 44 patients. Three additional courses of therapy were also judged to be appropriate due to documented signs and symptoms associated with urinary tract infections, despite cultures with less than 10(5) colony forming units per mL urine. Reasons for inappropriate use in the remaining seven patients included isolation of fewer bacteria than required by the criteria in asymptomatic patients (3 cases), isolation of organisms not sensitive to norfloxacin (1 case) and lack of dosage adjustment for renal insufficiency (3 cases). Nineteen of 32 evaluable inpatients (59%) received norfloxacin when a less expensive, equally effective agent was available. Although savings from more cost-effective therapy of urinary tract infections are minimal, due to the potential emergence of resistant organisms, norfloxacin should be reserved for infections not amenable to treatment with other oral antibiotics.

[Recombinant human erythropoietin in the treatment of anemic patients undergoing chemotherapy for cancer]. / Kemoterápiában részesülö vérszegény daganatos betegek kezelése rekombináns humán erythropoetinnel.

Twenty-seven anemic patients with malignant tumour who received chemotherapy were treated with recombinant human erythropoietin (r-HuEPO). The objective of this study was to evaluate the effect of r-huEPO on hematologic and quality of life parameters as well as on transfusion requirement in patients with anemia secondary to cancer and cyclic chemotherapy. Patient population was allocated into two groups based on the chemotherapeutic regimens: 1. cisplatin containing and 2, non cisplatin containing regimen. Using 2 g/dl increase in haemoglobin levels as the criteria for response, twenty women responded to r-huEPO treatment. The response was more marked in the cisplatin group. R-huEPO treatment saved transfusion in both groups. Again, less patients required transfusion among those treated with cisplatin. There was a marked improvement in the quality of life which was more pronounced in patients who responded to r-huEPO treatment and in those receiving non cisplatin chemotherapy. No serious adverse experiences occurred. In conclusion, two third of patients with anemia secondary to cancer and cyclic chemotherapy can be effectively treated with r-huEPO. R-huEPO treatment invariably saves transfusion and is highly effective in improving quality of life. Adverse reaction is exceptional.

Drug therapy of hypertensive crises.

The clinical features, pathogenesis, and pharmacologic management of hypertensive crises are reviewed, with emphasis on newer therapies. Hypertensive crises may be divided into hypertensive emergencies and hypertensive urgencies. Hypertensive emergencies, in which acute organ damage exists, require blood pressure reduction within one hour. In hypertensive urgencies no acute end-organ damage has yet occurred; however, blood pressure should be controlled within 24 hours. Factors that may precipitate a hypertensive crisis include renovascular hypertension, acute glomerulonephritis, head injuries, renin- or catecholamine-secreting tumors, antihypertensive-therapy withdrawal syndromes, eclampsia, and ingestion of tyramine by patients receiving monoamine oxidase inhibitors. The traditional drug of choice for therapy of hypertensive emergencies is sodium nitroprusside. Intravenous labetalol produces a prompt, controlled reduction in blood pressure and is a promising alternative. Other agents used are diazoxide, trimethaphan camsylate, hydralazine, nitroglycerin, and phentolamine. However, all these agents have disadvantages, including unpredictable antihypertensive effects, difficult blood pressure titration, and serious potential adverse effects such as profound hypotension, reduced renal blood flow, and increased myocardial workload. Most patients with hypertensive urgencies can be effectively treated with orally or sublingually administered agents. Older regimens of reserpine, methyldopa, or guanethidine, with their slow onsets and long durations of action, have been largely replaced by clonidine and nifedipine. Captopril and minoxidil have also been used with some success. Despite the lack of comparative trials with traditional agents, demonstrated efficacy and desirable pharmacologic characteristics have made several new agents acceptable for therapy of hypertensive crises.

Pharmacologic management of Paget's disease.

The pathogenesis, clinical features, indications for therapy, and current pharamacologic management of Paget's disease are reviewed. Paget's disease is a bone disorder of unknown etiology primarily affecting the elderly. Overactive bone resorption leads to the accelerated formation of disorganized, weak bone. Pain and fractures are common clinical features. Neurologic, cardiovascular, metabolic, and neoplastic complications are also reported. Because most patients are asymptomatic, the disease is often detected during routine roentgenography or laboratory tests. Primary indications for pharmacologic intervention include bone pain, neural compression, immobilization hypercalcemia or hypercalciuria, cardiac failure, and orthopedic surgery. Recurrent or non-healing fractures and rapidly progressing complications are additional indications. Drugs used in the management of Paget's disease include calcitonin, etidronate disodium, and plicamycin. Although these agents are efficacious, each has disadvantages. Clinical resistance to animal calcitonins may develop, and the cost of therapy may be prohibitive. Etidronate may induce ostemalacia. The use of plicamycin is limited by potentially severe toxicities. Dichloromethylene and aminohydroxypropylidene are promising diphosphonate compounds but are still investigational In those patients who are unresponsive to single-agent regimens, combination therapy may prove effective. Although many patients with Paget's disease do not require pharmacologic therapy, calcitonin and etidronate are the agents of choice when it is indicated.