[Medication adherence in asthma therapy--a structured review]. / Medikamentenadhärenz in der Asthmatherapie--eine strukturierte Übersicht.

BACKGROUND: The adherence level of Asthma therapy is low. We provide a literature overview about the determinants of adherence in asthma therapy, and potential options that lead to an improvement of adherence. We also discuss cost issues of poor adherence. METHODS: A systematic literature search was conducted and 53 articles were identified. RESULTS: The most prominent driving factors of adherence are patient beliefs, comorbidities, physician-patient relationship, and medication regimen. The cost effectiveness of adherence improving measures has yet to be shown. CONCLUSION: As asthma control is primarily depended on adherence, cost effective adherence programs need to be developed that respond to patients' individual needs.

Novel temperature dependent tensile test of freestanding copper thin film structures.

The temperature dependent mechanical properties of the metallization of electronic power devices are studied in tensile tests on micron-sized freestanding copper beams at temperatures up to 400 °C. The experiments are performed in situ in a scanning electron microscope. This allows studying the micromechanical processes during the deformation and failure of the sample at different temperatures.

Identification and characterisation of a novel KCNQ1 mutation in a family with Romano-Ward syndrome.

Romano-Ward syndrome (RWS), the autosomal dominant form of the congenital long QT syndrome, is characterised by prolongation of the cardiac repolarisation process associated with ventricular tachyarrhythmias of the torsades de pointes type. Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequence analysis have identified a KCNQ1 mutation in a family that were clinically conspicuous due to several syncopes and prolonged QTc intervals in the ECG. The mutant subunit was expressed and functionally characterised in the Xenopus oocyte expression system. A novel heterozygous missense mutation with a C to T transition at the first position of codon 343 (CCA) of the KCNQ1 gene was identified in three concerned family members (QTc intervals: 500, 510 and 530 ms, respectively). As a result, proline 343 localised within the highly conserved transmembrane segment S6 of the KCNQ1 channel is replaced by a serine. Co-expression of mutant (KCNQ1-P343S) and wild-type (KCNQ1) cRNA in Xenopus oocytes produced potassium currents reduced by approximately 92%, while IKs reconstitution experiments with a combination of KCNQ1 mutant, wild-type and KCNE1 subunits yielded currents reduced by approximately 60%. A novel mutation (P343S) identified in the KCNQ1 subunit gene of three members of a RWS family showed a dominant-negative effect on native IKs currents leading to prolongation of the heart repolarisation and possibly increases the risk of malign arrhythmias with sudden cardiac death.

[Interdisciplinary management of pregnant women with connective tissue diseases]. / Interdisziplinäre Betreuung von schwangeren Patientinnen mit Kollagenosen.

Connective tissue diseases affect frequently women during the childbearing period. As fertility is not considerably reduced in these patients, monitoring and treatment of a pregnant patient is a complex clinical setting that requires an intensive cooperation between gynecologists, rheumatologists and pediatricians. In this article, a 4-point-program for the clinical management of these patients is presented that addresses specifically the problems inherent with the identification of patients with connective tissue diseases, preconceptional diagnostics as well as monitoring and treatment during pregnancy and the postpartal period. Clinical aspects that are intensively discussed include immunosuppressive therapy during pregnancy, the management of antiphospholipid antibody-dependent problems and the prophylaxis and treatment options for congenital heart block.

Relation between depression and anxiety in dystonic patients: implications for clinical management.

Past clinical research has identified depression as the most common psychiatric disorder associated with cervical dystonia (CD). The purpose of our study is to document different patterns of psychopathology, the frequency of psychiatric disorders, and possible correlation with the neurological disorder in patients with CD. Forty patients with CD were investigated to assess levels of psychopathology on two self-rated scales: the Beck Depression Inventory (BDI) and Symptom Check List (SCL-90). To determine the presence of psychiatric disorders, the patients were evaluated using the standard instrument in the DSM-III-R (Structured Clinical Interview Schedule, SCID). A small group of dystonic patients (12%) had higher levels of psychopathology, with significant amounts of concomitant anxiety and depression on the BDI and SCL-90. SCID criteria for at least one psychiatric disorder were fulfilled in 22 patients (55%), including both the lifetime and current diagnoses. The most frequent diagnostic categories were anxiety (40%) and major depressive disorders (37.5%). In 17 patients (42.5%), criteria for at least one lifetime diagnosis were fulfilled prior to the onset of CD. Psychiatric evaluation does not indicate one specific disorder associated with CD. The presence of anxiety and depression symptoms before and during the course of dystonia, without a possible causal relationship, could mean that the alteration of a chain of physiological events in the central nervous system may not lead to a single clinical picture. The relatively high overall lifetime prevalence of anxiety and depressive disorders may indicate the need for a broader diagnostic and therapeutic approach to patients with focal dystonia.

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Effects of prostaglandin E1, dobutamine and placebo on hemodynamic, renal and neurohumoral variables in patients with advanced heart failure.

Excessive neurohumoral activity remains a major burden to the circulation of patients with advanced heart failure. Prostaglandin E1 (PGE1), a balanced i.v. vasodilator, was shown to elicit favorable hemodynamic and clinical effects in this cohort. A prospective randomized parallel group trial was performed to evaluate acute, intermediate and chronic changes in hemodynamic, neurohumoral and renal variables in response to PGE1, dobutamine and placebo. Thirty patients with class III and IV heart failure and low cardiac index (mean 1.9 l/min/m2) two hours after oral drugs including high dose enalapril were included. A 7-day-infusion of PGE1 (16.5 +/- 5 ng/kg/min, range 10 to 20 ng/kg/min, group A n = 10), dobutamine (4.5 +/- 1 micrograms/kg/min, range 2.5 to 5 micrograms/kg/min, group B n = 10) or placebo (saline, group C n = 10) was administered via a central venous access line after stepwise titration until intolerable side effects developed with PGE1 or a 20% increase in cardiac index occurred with dobutamine, which was continued on this dose throughout while PGE1 was maintained on 50% peak dose. Hemodynamic data were collected at baseline, at peak dosages, after 12 hours and after 7 days. Of neurohumoral variables plasma norepinephrine, big endothelin (Big ET) and atrial natriuretic peptide (ANP) were simultaneously evaluated using RIA methods. Renal plasma flow (by paraaminohippurate clearance) and glomerular filtration rate (by iothalamate clearance) was measured prior to and during the infusions (after 12 hours and after 7 days). At peak dose and at 12 hours significant drops from baseline of mean pulmonary artery pressure, pulmonary capillary wedge pressure and systemic vascular resistance were observed which were accompanied by a rise in cardiac output with both PGE1 and dobutamine. These changes were maintained through 7 days when pulmonary vascular resistance levels also fell with both active drugs. Blood pressure did not change throughout, but PGE1 increased heart rate slightly at 12 hrs. Both PGE1 and dobutamine enhanced renal plasma flow after 7 days, but only PGE1 decreased glomerular filtration fraction significantly. Glomerular filtration rate did not change with either drug. PGE1 decreased ANP levels at 12 hrs, and dobutamine increased big ET levels at peak, but decreased big ET at 7 days. Norepinephrine levels were unaffected throughout. Except a slight decrease in right atrial pressure after 7 days placebo did not change any measured variable significantly. Taken together, these data suggest that treatment with PGE1 is as efficacious as low-dose dobutamine in improving cardiac performance and renal perfusion in advanced heart failure. Of importance, no deleterious neurohumoral counterregulation was observed with PGE1.

Primary colon cancer without gross mucosal tumor: unusual presentation of a common malignancy.

Colon cancer typically arises in the colonic lumen, allowing for endoscopic detection of cancerous and premalignant lesions. In the case presented, a 73-year-old man with iron deficiency anemia had two colonoscopies showing only diverticula and internal hemorrhoids. Three years later, when the patient complained of dull, intermittent lower abdominal pain, a third colonoscopy identified diverticula, three adenomatous polyps, and no other abnormality. Computed tomography (CT) of the abdomen revealed a 5 cm x 6 cm pericolic fluid collection, which was later found to communicate with the sigmoid colon. The surgical specimen from a partial colectomy contained a distal sigmoid perforation with a 2.5 cm moderately differentiated adenocarcinoma in the underlying submucosal tissue. There was no gross intraluminal tumor. Histopathology, including immunohistochemistry, was consistent with colonic adenocarcinoma. Primary colon cancer grossly sparing the mucosa is an unusual presentation for this common malignancy.

Psychiatric comorbidity in patients with spasmodic torticollis.

Several studies have reported raised levels of psychopathology based on self-rating scales in patients with spasmodic torticollis. Recent publications have also proposed that psychopathology, especially symptoms of depression, might be a reaction to dystonia or constitute a nonspecific reaction pattern. To determine the actual frequency of psychiatric disorders, we evaluated 44 patients with spasmodic torticollis (20 female, 24 male; mean age 43.6 years, SD 10.4) using the standard instrument for psychiatric diagnosis in the DSM-III-R (Structured Clinical Interview Schedule, SCID). The SCID permits retrospective diagnosis for most of the major psychiatric disorders, including the time before onset of dystonia. SCID criteria for at least one psychiatric disorder were fulfilled in 65.9% of patients, including both lifetime and current diagnosis. The most frequent diagnostic categories were panic disorder with or without agoraphobia (29.5%), major depressive disorder (25%), substance abuse (13.6%), and obsessive compulsive disorders (6.8%) were diagnosed less frequently. The patient-recalled onset of psychiatric symptoms preceded onset of torticollis symptoms in 43.2% of those investigated.

Relationship between kidney function, hemodynamic variables and circulating big endothelin levels in patients with severe refractory heart failure.

UNLABELLED: Fluid retention is a major characteristic of symptomatic, progressive heart failure when a main factor implicated in the pathogenesis of renal dysfunction is renal hypoperfusion. This may be a consequence of forward cardiac failure, resulting in a low cardiac output integrating poor left ventricular function secondary to myocardial impairment and increased resistance in the regional renal vasculature secondary to locally released vasoconstrictors, e.g. endothelin. So far, the role of the pulmonary circulation in perpetuating renal dysfunction in heart failure is unclear. METHODS: We investigated the relationship of hemodynamic variables obtained during right heart catheterization and plasma big endothelin levels to renal function variables in 18 male patients aged 52 +/- 3 years, with heart failure in the NYHA function class III-IV, based on idiopathic causes in 8 and ischemic causes in 10 patients. Renal plasma flow (RPF) was established by paraaminohippurate (PAH) clearance and the glomerular filtration rate (GFR) was measured by iothalamate clearance. RESULTS: Plasma big endothelin (ET) levels were increased above the upper normal range (1.8 fmol/ml) in 16 out of 18 patients, averaging 5.0 +/- 0.8 fmol/ml (1.7-11.9 fmol/ml). Positive correlations to big ET plasma levels were detected with mean pulmonary pressure (r = 0.73, p < 0.001) pulmonary capillary wedge pressure (r = 0.56, p < 0.05) and pulmonary vascular resistance index (r = 0.69, p < 0.01). Glomerular filtration rate (70 +/- 7 ml/min) and renal plasma flow (358 +/- 36 ml/min) were considerably reduced and exhibited a tendency to correlate inversely with big ET levels (r = -0.46, p = 0.056 and r = -0.44, p = 0.069, respectively). Contrary to expectations, RPF did not correlate significantly with cardiac index, systemic vascular resistance index or arterial blood pressure. In contrast, significant correlations were detected of RPF with pulmonary capillary wedge pressure (r = -0.69, p < 0.01), mean pulmonary artery pressure (r = -0.65, p < 0.01), right atrial pressure (r = -0.47, p < 0.05) and right ventricular ejection fraction (r = 0.49, p < 0.05). CONCLUSION: The findings suggest a role for endothelin in renal vasoconstriction and accord well with the concept that in severe heart failure renal hypoperfusion--by volume retention--as well as increased endothelin synthesis--by pulmonary vasoconstriction--play a part in the increased pulmonary filling pressures.

Central nervous system function after cardiopulmonary bypass.

In a prospective study, an elderly group of patients (n = 63, 47 male, 16 female, age 40-65 years) was examined before and after open-heart surgery under cardiopulmonary bypass: postoperatively, 19 patients (30%) showed no clinical neuropsychiatric symptoms, whereas in 35 patients (56%) mild or transient neurological signs and in nine (14%) severe neurological complications were found. The postoperative EEG changes were characterized by a slight delta-theta increase, an alpha decrease and a significant slowing of the dominant frequency from 9.7 to 9.3 Hz. In brainstem auditory evoked potentials no changes were found, and in somatosensory evoked potentials (median nerve) the latency of the early cortical component, N20, increased. Cardiovascular reflexes showed increased changes, similar to those found in autonomic neuropathies. In the neuropsychological test battery, the Visual retention test (Benton) and the Rorschach test showed slight postoperative improvement, whereas other psychometric variables (flicker fusion frequency, reaction time) did not change. Despite an improved operative technique some minor clinical and neurophysiological disturbances of the central nervous system remain. However, specific pre- or peri-operative risk factors for these postoperative disturbances or complications could not be identified.

[Effects of carotid endarterectomy on various neuropsychologic parameters. A neuropsychologic longitudinal study]. / Einflüsse der Karotisendarterektomie auf verschiedene Hirnleistungsparameter. Eine neuropsychologische Längsschnittstudie.

Carotid endarterectomy was performed in 25 patients with symptomatic cerebrovascular disease. All patients underwent detailed neuropsychological investigations immediately before surgery, immediately after surgery, and again after a follow-up period of 14 months. Immediately after surgery the flicker fusion frequency was temporarily reduced, indicating an impairment of global cognitive functioning. Postoperatively, verbal attention was found to be improved, particularly in younger patients, in patients with TIA, and in patients with left-sided operation. Finally, visual retention (Benton) was improved at the end of the observation period, especially in older patients and in patients with left-sided operation. Considering the complexity of pathologic brain perfusion, the effects of carotid endarterectomy can only be explained if a multidimensional approach is adopted.

Automated measurement of cell destruction: the Patimed system in comparison with conventional HLA typing and the cell mediated lympholysis test (CML).

The key role of HLA polymorphism in the pathogenesis of many diseases and in determining compatibility in transplantation makes it desirable to employ automated systems for identifying HLA polymorphism. For more than one year we have used the photometer system Patimed commercially available from the Leica company. We compared the results of the conventional cell-mediated lympholysis test and conventional serological HLA typing with the results obtained by the Patimed system. Despite some good preliminary results it would be premature, in our opinion, to recommend the Patimed system for routine assessment of killer cell activity whereas we can definitely recommend the Patimed system to define HLA class I and class II molecules serologically for research or routine purposes.

[Automated measurement of cell destruction with the Patimed System in comparison with conventional HLA typing]. / Automatisiertes Messen der Zelldestruktion mit dem Patimed-System im Vergleich zur konventionellen HLA-Typisierung.

HLA molecules serve as identity markers for immunocompetent cells which respond to pathogens and transplant tissue antigens to distinguish self from non-self. The continuous discovery of new HLA polymorphisms which are associated with various diseases or are involved in graft rejection continuously increases the number of HLA antigens which need to be identified for each individual. We defined the HLA class I and HLA class II antigens with the NIH standard microcytotoxicity system and compared the results with those obtained using the commercially available automated Patimed system. Our results show that serological identification of HLA antigens with the Patimed system is reliable. It can be recommended for routine as well as for research purposes.

[Methods of neuropsychologic functional adaptation training in central speech disorders]. / Zur Methode des neuropsychologischen Funktionseinstimmungstrainings zentraler Sprachstörungen.

"Funktionseinstimmungstraining--FET" (functional adaptation training) includes exercises aiming reorganization of verbal communication, improvement of capacity of concentration, vigilance, mental faculty over a longer period of time and memory. Following exact examination of speech deficits and accurate clinical-neuropsychological investigation, a certain program of training is established for each patient individually. Effects of FET might be diagnosed during the training-sessions as well as after the final set up of rehabilitation by means of objective data.

Impairment of motor planning in patients with Parkinson's disease: evidence from ideomotor apraxia testing.

Compared with a group of age matched controls, patients with Parkinson's disease scored significantly lower in testing for ideomotor apraxia. Imitation of movement sequences was affected more severely than performance of single movements. The degree of impairment was not related to severity of motor disability, but correlated strongly with the results of tests that measured visuospatial and visuoperceptive abilities. It is suggested that defective encoding and central processing of visuospatial information impairs memory for movement which is necessary for correct imitation of movements. Enhanced vulnerability to interference between successively presented items may cause further deterioration of performance in the copying of movement sequences.

Apraxia of the left limbs in a case of callosal disconnection: the contribution of medial frontal lobe damage.

A 40 year old right-handed woman suffered hemorrhage from an anterior cerebral artery aneurysm. CT scan showed destruction of the anterior two thirds of the corpus callosum, both cingulate gyri, and the white matter underlying the medial frontal lobes. The left limbs displayed apraxia on verbal command, in imitation, and in actual object use. There were antagonistic actions of both hands, and the patient accused her left hand of disobeying her. We interpret the leftsided apraxia as resulting from a lack of interhemispheric transfer combined with a deficit in ipsilateral motor control stemming from damage to the left supplementary motor area. Right frontal lobe damage may have impaired the motor learning capacity of the right hemisphere and thus its ability to compensate for the lack of left hemisphere motor control.