[Pulmonary necrotizing sarcoid granulomatosis in a patient with primary biliary cirrhosis]. / Nekrotisierende sarkoidale Granulomatose der Lunge bei einer Patientin mit primärer biliärer Leberzirrhose.

HISTORY AND ADMISSION FINDINGS: A 53-year-old woman presented with recurrent episodes of cough and non-specific pulmonary symptoms. For many years she had been known to have primary biliary cirrhosis. INVESTIGATIONS: The chest X-ray showed multiple pulmonary nodules. Microbiological examination did not detect any pathogen and transbronchial biopsy of the pulmonary nodules failed to provide a diagnosis. Histology of a surgical lung biopsy showed interstitial inflammation, vasculitis and non-caseating granulomas. TREATMENT AND COURSE: The findings indicated necrotizing sarcoid granulomatosis. During oral corticoid therapy the pulmonary nodules regressed within a few weeks. The patient has remained free of pulmonary symptoms. CONCLUSION: Pulmonary necrotizing sarcoid granulomatosis is a rare condition to consider in the differential diagnosis of pulmonary nodules. Because of the histological findings and its benign course it resembles sarcoidosis.

Trapidil decreases the aggregation of platelets from heart transplant recipients ex vivo.

Heart transplant recipients show platelet hyperaggregability, which may be related to the incidence of graft vasculopathy. We investigated whether trapidil can inhibit the aggregation of platelets from these patients. Platelet count, mean platelet volume (MPV), and adenosine diphosphate (ADP)-induced platelet aggregation were determined in 18 heart transplant recipients and 12 healthy subjects. Additionally, platelet-rich plasma from the patients was incubated with trapidil or with saline, prior to measuring ADP-induced aggregation. The MPV was significantly greater in patients compared to controls (9.4+/-1.1 vs 8.5+/-0.7 fL; P=.01), and ADP-induced platelet aggregation was significantly increased in patients compared to controls (81.2%+/-13.1% vs 69.6%+/-16.2%; P=.04, respectively). The trapidil-treated samples showed significantly decreased platelet aggregation compared to the control samples (24.2%+/-12.6% vs 66.7%+/-11.7%; P<.001). Platelets from heart transplant recipients showed an increased MPV and increased ADP-induced aggregation. Trapidil effectively reduced the ADP-induced aggregation ex vivo.

[Proximal fracture of the femur in elderly patients. The influence of surgical care and patient characteristics on post-operative mortality]. / Die proximale Femurfraktur des älteren Patienten. Einfluss von operativer Versorgung und Patientencharakteristika auf die postoperative Letalität.

In a retrospective study, 1.173 fractures of the proximal femur, which had been treated surgically, were analysed in two periods from 1975 to 1991 and from 1992 to 2000. The influence on mortality of preoperative risk factors and primary treatment with total hip replacement (THR), even in cases of pertrochanteric fractures, was analysed by stepwise logistic regression. In the later period, mortality within 90 days was 13.1%, and within 1 year 22.2%. Rejection of hemiendoprosthesis in high-risk patients with intracapsular fractures increased the mortality rate from 6.3% to 11.8%. The introduction of dynamic hip screws instead of Ender nails led to a reduction of mortality from 16.5 to 7.1%. Higher mortality after THR (27.6%) compared to osteosynthesis (15.5%) in pertrochanteric femur and lateral neck fractures was due to higher age and increased risk factors. Although the influence of some risk factors could be reduced, age, sex and morbidity influenced the outcome more than surgical treatment. THP, even after pertrochanteric fractures, is reasonable if it guarantees a quick and enduring mobilisation of the patient. Bicentric bipolar prostheses are recommended for high risk patients.

Effect of radiofrequency ablation on atrial myocardium.

OBJECTIVES: Successful RF ablation of atrial fibrillation supposedly requires the creation of continuous linear lesions. This study aimed to determine the potential role of functional modifications of atrial myocardium in the vicinity of anatomic RF lesions. METHODS: In 10 normal beagles (group A), a multiplexer mapping system and an epicardial multi-electrode were used to reconstruct atrial activation patterns during pacing at two cycle lengths before and after attempts to induce two linear right atrial lesions with a standard ablation catheter, respectively. An intercaval "drawback" was repeated 3 times over 5 min at a set temperature of 70 degrees C, followed by a transversal "point-by-point" ablation from the interatrial septum to the right-lateral tricuspid annulus at 70 degrees C/60 s each. Induction of atrial flutter was attempted before and after each ablation. In another 6 beagles (group B), a high-resolution multi-electrode was used to study epicardial functional effects resulting from single endocardial RF lesions on the free right atrial wall. Using three energy settings (60 degrees C/30 s, 60 degrees C/60 s, 70 degrees C/60 s), activation patterns were analyzed at two cycle lengths and local effective refractory periods were measured across the lesion. RESULTS: The lesions induced in group A only marginally affected atrial activation patterns and total activation times. However, as shown in dogs with atrial flutter, regional slow conduction was enhanced and functional conduction blocks were facilitated at high atrial rates, resulting in a significant prolongation in the revolution time of respective reentrant circuits. Apart from inducing anatomic lesions, single endocardial RF lesions (group B) were shown to delay epicardial conduction in adjacent myocardium in an energy- and rate-dependent way. Furthermore, an energy-dependent prolongation of effective refractory periods by far exceeding the size of anatomic lesions was observed. CONCLUSIONS: Continuous linear atrial lesions are hard to achieve with conventional ablation techniques. However, RF lesions induce changes in conduction and refractoriness around the anatomic lesion, which are likely to contribute to the overall effect of respective therapeutic interventions.

Effects of propafenone on anisotropic conduction properties within the three-dimensional structure of the canine ventricular wall.

BACKGROUND: Structural complexities of the intact ventricular wall cause a very complex spread of activation. The effects of regional tissue damage and of antiarrhythmic drugs on directional differences in activation should help to further elucidate intramural conduction patterns. METHODS AND RESULTS: In 10 healthy dogs and in 5 dogs with subacute anterior wall infarction, 6 parallel rows of 6 needle electrodes with 4 bipolar electrode pairs per needle were inserted into the left anterior ventricular wall. Using a computerized multiplexer-mapping system, the spread of activation in epi-, endo- and midmyocardial muscle layers and in the surviving epicardium, respectively, was reconstructed. Marked differences in conduction velocities relative to fiber orientation were evident in the surviving epicardium of infarcted hearts. Directional differences in conduction velocities, although less pronounced, were still preserved throughout the intact ventricular wall. Epicardial transverse conduction in intact hearts was significantly faster than transverse conduction in infarcted hearts (0.87 +/- 0.11 m/s vs 0.68 +/- 0.1 m/s). In normal hearts, propafenone (2 mg/kg) decreased conduction velocities primarily in longitudinal directions (-27 +/- 10%), but also moderately in transverse directions (-13 +/- 7 %) of all muscle layers, with no significant effect on straight (-4 +/- 8 %), but on oblique transmural conduction (-33 +/- 18 %). In infarcted hearts propafenone decreased conduction particularly in longitudinal direction (-23 +/- 14 %) without affecting conduction transverse to the fiber orientation (+3 +/- 6%). CONCLUSIONS: Longitudinal intramural shortcircuits reduce directional differences in activation. Transmural infarction results in a loss of alternative intramural pathways, unmasking marked anisotropy in the surviving epicardium. Conduction delay in intramural pathways explains the effects of propafenone on transverse and oblique transmural conduction. Primarily longitudinal conduction delay results in reduced tissue anisotropy.

Intercaval block in normal canine hearts : role of the terminal crest.

BACKGROUND: The intriguing monotony in the occurrence of intercaval conduction block during typical atrial flutter suggests an anatomic or electrophysiological predisposition for conduction abnormalities. METHODS AND RESULTS: To determine the location of and potential electrophysiological basis for conduction block in the terminal crest region, a high-density patch electrode (10x10 bipoles) was placed on the terminal crest and on the adjacent pectinate muscle region in 10 healthy foxhounds. With a multiplexer mapping system, local activation patterns were reconstructed during constant pacing (S(1)S(1)=200 ms) and introduction of up to 2 extrastimuli (S(2), S(3)). Furthermore, effective refractory periods were determined across the patch. If evident through online analysis, the epicardial location of conduction block was marked for postmortem verification of its endocardial projection. Marked directional differences in activation were found in the terminal crest region, with fast conduction parallel to and slow conduction perpendicular to the intercaval axis (1.1+/-0.4 versus 0.5+/-0.2 m/s, P<0.01). In the pectinate muscle region, however, conduction velocities were similar in both directions (0.5+/-0.3 versus 0.6+/-0.2 m/s, P=NS). Refractory patterns were relatively homogeneous in both regions, with local refractory gradients not >30 ms. During S(3) stimulation, conduction block parallel to the terminal crest was inducible in 40% of the dogs compared with 0% in the pectinate muscle region. CONCLUSIONS: Even in normal hearts, inducible intercaval block is a relatively common finding. Anisotropic conduction properties would not explain conduction block parallel to the intercaval axis in the terminal crest region, and obviously, refractory gradients do not seem to play a role either. Thus, the change in fiber direction associated with the terminal crest/pectinate muscle junction might form the anatomic/electrophysiological basis for intercaval conduction block.

[Predictive value of frequency, duration and rate of ventricular salvos in ambulatory ECG for inducibility of sustained ventricular tachycardia]. / Prädiktiver Wert der Frequenz, der Dauer und der Häufigkeit ventrikulärer Salven im Langzeit-EKG für die Induzierbarkeit anhaltender Kammertachykardien.

Identification of high risk patients with coronary artery disease (CAD) prone to sudden cardiac death still remains a difficult issue. In 211 patients with CAD diagnosed by coronary angiography and documented non-sustained ventricular tachycardia (NSVT), programmed ventricular stimulation (PVS) was performed. NSVTs documented during Holter monitoring were analysed concerning frequency, duration and rate. To relate those parameters to the inducibility of sustained monomorphic ventricular tachycardias (MVT) during PVS, the total population was divided in different groups; patients with 1, 2-5 or > 5 salvos within 24 h; patients having salvos with a rate of > or = 150/min or < 150/min; patients with 3-5, 6-10 or > 10 consecutive extra beats. It could be demonstrated that in patients with CAD and NSVTs, induction of MVTs during PVS is more likely if the rate of the spontaneously occurring NSVT is > or = 150/min (22.1 vs 8.9%; p = 0.042). In contrast, there is apparently no correlation between the duration and incidence of NSVTs and the prevalence of MVTs during PVS. Multivariate analysis revealed the rate of documented NSVTs (odds ratio 2.98, p = 0.0314) and a decrease of left ventricular ejection fraction (odds ratio 1.69; p = 0.0013) as independent risk factors for the inducibility of MVTs. Conclusions CAD patients with fast salvos (> or = 150 beats/min) and reduced left ventricular ejection fraction are more likely to reveal inducible MVT during PVS and should, therefore, preferably be subjected to invasive risk stratification. The number of salvos per day and the number of consecutive beats, on the other hand, do not seem to be of relevant predictive value.

Multisite pacing for prevention of atrial tachyarrhythmias: potential mechanisms.

OBJECTIVES: To determine the effects of single-, dual-, triple- and quadruple-site atrial pacing on atrial activation and refractoriness in normal canine hearts. BACKGROUND: Multisite pacing has been suggested to be superior to single-site pacing for prevention of atrial tachyarrhythmias. However, the underlying electrophysiological mechanisms are undetermined at the moment, as is the rationale for the selection of pacing locations and the number of pacing sites. METHODS: In 13 normal beagle dogs, an epicardial multielectrode (128 bipoles) and a multiplexer mapping system were used to reconstruct epicardial atrial activation patterns obtained during simultaneous stimulation from up to four electrodes located in the high and low right and left atrium, respectively. For all pacing modes (single-, dual-, triple- and quadruple-site pacing), total activation times and local effective refractory periods at eight randomly selected sites as well as local recovery intervals were determined. In a subgroup of five dogs, total epicardial activation times were also obtained during single-site septal stimulation (septal group). RESULTS: Activation times and local recovery intervals were minimized by triple-site stimulation, whereas a fourth site did not produce further shortening. Septal stimulation produced epicardial activation times comparable to quadruple-site stimulation. Local refractory periods and their dispersion always remained unaffected. Functional conduction blocks apparent during single-site were found to resolve during multisite stimulation. CONCLUSIONS: Multisite pacing can prevent functional conduction blocks by multidirectional excitation and a reduction in total activation time. Triple-site and, possibly, septal pacing modes are expected to be most efficient because both minimize total activation times and maximize the multidirectionality of excitation. In spite of unaffected local refractory periods, the shortening of local recovery intervals might homogenize atrial repolarization and, thus, contribute to the preventive effects of multisite pacing.

[Evaluation of syncope in geriatric patients: normal values, complications and outcome of invasive electrophysiological study]. / Synkopenabklärung bei geriatrischen Patienten: Normalwerte, Komplikationen und Ergebnisse der invasiven elektrophysiologischen Untersuchung.

Invasive electrophysiologic study (EPS) is an important tool in the assessment of patients with unexplained syncope. Especially in the elderly, the need for a complete diagnostic work-up is counterbalanced by the fear of complications associated with invasive procedures. Thus, the present study specifically addressed the question whether the risk/benefit ratio of EPS in geriatric patients with unexplained syncope justifies this invasive procedure. An invasive EPS was performed in 96 patients between 70 and 80 years and 21 patients older than 80 years. The control group consisted of 65 patients younger than 40 years. With increasing age, the diagnostic yield of EPS also increased (positive EPS finding in 20% of the control group and in 54% of the oldest patients). The majority of complications were of minor clinical significance and no significant differences were found between the three groups. Finally, no age-related difference in measured standard electrophysiological parameters was evident. Due to the high diagnostic value and the low complication rate, EPS can be recommended in elderly patients with unexplained syncope. An age-specific standardization of electrophysiologic parameters, measured during EPS, does not seem to be required.

Stereoselective disposition of the enantiomers of the benzoquinolinone LY191704, a human type I 5 alpha-reductase inhibitor. Differences between rats and dogs.

The benzoquinolinone LY191704, a potent and selective human type I 5 alpha-reductase inhibitor, is a racemic mixture of the compounds LY300502 and LY300503. Rats were treated orally with 10, 30, or 100 mg of LY191704/kg/day for 1 month. Plasma concentrations of LY191704 increased with dose. Both the AUC and maximal concentration values were reduced at 30 and 100 mg/kg on the last day, compared with the first day of treatment. In rat plasma the ratio of LY300502 to LY300503 ranged from 1.6 to 2.0 after the first dose and from 1.6 to 2.4 after the last dose. In dogs administered the same daily oral doses of LY191704 for 1 month, the plasma ratio of LY300502 to LY300503 was essentially unity at the beginning and end of the study. After daily oral administration of LY300502 or LY300503 to rats, at 30, 100, or 300 mg/kg for 14 days, the mean dose-normalized AUC value for LY300503 was 56% of that for LY300502 after the first dose and 38% after the last dose. The rate of metabolic oxidation for LY300502 in rat liver microsomes was approximately 32% of that for LY300503, whereas no differences were observed in the metabolism of the enantiomers in dog liver microsomes. The differences observed between LY300502 and LY300503 were attributed to preferential metabolism of LY300503 in rats. The data indicated that LY300503 was subject to a greater rate of metabolism than LY300502 and induced its own metabolism in rats and that the preferential metabolism of LY300503 was species-specific.

A scoring system for evaluating the condition of transported neonates.

A scoring system for the evaluation of the clinical status of transported small premature infants was modified to make it applicable to the evaluation of both premature and term infants. Blood glucose concentration, systolic blood pressure, blood pH and PO2, and body temperature were assessed and given scores of 0, 1 or 2 for abnormal, borderline and normal values, respectively. The scoring system was used for quality assurance studies of changes in patient status during transport from community hospitals to the neonatal intensive care unit and proved useful in identifying inadequate attention to body-temperature maintenance. The scoring system showed an improvement in the criterion after changes in clinical monitoring and management of body temperature were instituted. An additional use of the scoring system was for the identification of specific problems in neonatal stabilization in referring community hospitals.

Gravitational forces on the chest wall.

The gravitational work of breathing was determined by measuring the vertical motion of body mass. The subject, seated or lying supine on a force platform, performed breathing maneuvers in which rib cage volume (Vrc) and abdominal volume (Vab) were changed in varying proportions. The increment in the vertical force exerted on the platform and Vrc and Vab were measured over the course of each maneuver. The force signal was integrated twice with respect to time to obtain the change in the product of mass and height of the subject. This was multiplied by the gravitational acceleration to obtain the change in the gravitational potential (Ug). Simultaneous values of Ug, Vrc, and Vab were taken from the data, and the values of the coefficients for which the following equation best fit these values were determined: Ug = a1 Vrc + a2 Vab + (1/2)a11 Vrc2 + a12 Vrc Vab + (1/2)a22 Vab2. The coefficients a1 and a2 can be interpreted as the values of the expiratory gravitational forces on the rib cage and abdomen, respectively. In the seated posture, the force on the rib cage is expiratory and the force on the abdomen is inspiratory; the magnitudes of both are approximately 8 cmH2O. In the supine posture, both are expiratory forces of approximately 9 cmH2O. The coefficients of the quadratic terms in Ug are all positive, and the gravitational work per unit volume of chest wall expansion increases with increasing volume in both postures. The coefficients of the quadratic terms can be interpreted as gravitational contributions to the elastances of the compartments.

Cleavage of synthetic peptides by purified poliovirus 3C proteinase.

Synthetic peptides, 14-16 residues in length, were used as substrates for purified recombinant poliovirus proteinase 3C. The sequences of the substrates correspond to the sequences of authentic cleavage sites in the poliovirus polyprotein, all of which contain Gln-Gly at the scissile bond. Specificity of cleavages was demonstrated by analysis of 3C digests of synthetic peptides. Relative rate constants for the cleavages were derived by competition experiments. The rate constants roughly correlated with the estimated half-life of the homologous precursor proteins detected in poliovirus-infected cells. The peptide most resistant to cleavage corresponded to the 3C/3D junction, a site known to be cleaved very slowly by 3C in vivo. Substitution of threonine for alanine in P4 position of this peptide, however, resulted in significant cleavage. This observation supports the hypothesis that the residue in P4 position, in addition to the Gln-Gly in P1 and P1', respectively, contributes to substrate recognition. Ac-Gln-Gly-NH2 was not a substrate for 3C.

Fiber stabilization of bent cylinders, with an application to intervertebral disks.

Fibers cannot carry compression, and reinforcing fibers in a cylinder can only carry load if they are kept taut by the deformations of the cylinder. In the present study it is found that in pure bending, deformations that change the pitch, i.e., the angle between the fibers and the cross-sectional plane, towards 30 deg will slacken the fibers. With an initial pitch different than 30 deg, fibers in one half of the cross section will then be slackened by bending, and this half of the cylinder becomes unstable. Applied to the mechanics of the intervertebral disks, this may help explain mechanisms leading to nucleus prolapse.

Neutrophil granulocyte function in the early diagnosis of acute myelomonocytic and myeloblastic leukaemia.

The phagocytic and bactericidal activities of neutrophil granulocytes from 5 patients with early acute myelomonocytic or myeloblastic leukaemia and 5 controls have been examined. In each patient the bactericidal activity was lower than in any control and the neutrophil dysfunction was demonstrated before leukaemia could be diagnosed from clinical and haematological findings. During periods of remission, the bactericidal activity was normal. Results of neutrophil granulocyte function studies may be a significant aid in the early diagnosis of acute myelomonocytic and myeloblastic leukaemia.