Beta glucan induces proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer.

AIM: Glucans are glucose polymers that constitute a structural part of fungal cell wall. They can stimulate the innate immunity by activation of monocytes/macrophages. In human studies it has been shown that beta glucan has an immunomodulatory effect and can increase the efficacy of the biological therapies in cancer patients. In this prospective clinical trial we assessed in vivo effects of short term oral beta glucan administration on peripheral blood monocytes and their expression of activation markers in patients with advanced breast cancer. METHODS: 23 female patients with advanced breast cancer were included in the study. Median age of the patients was 52 years. Sixteen healthy females with a median age of 48 years served as the control group for comparing the initial blood samples. Peripheral blood samples were drawn on day zero and patients started receiving oral 1-3, 1-6, D-beta glucan daily. Blood samples were recollected on the 15th day. In the initial samples mean lymphocyte count was significantly lower in the patients with breast cancer (1281+/-306/mm(3) versus 1930+/-573/mm(3), p=0.04). In the patients with breast cancer, mean monocyte count which was 326+124/mm(3) at the beginning, was increased to 496+194/mm(3) at the 15th day (p=0.015). Expression of CD95 (Apo1/Fas) on CD14 positive monocytes was 48.17% at the beginning, which was increased to 69.23 % at the 15th day (p=0.002). Expression of CD45RA on CD14 positive monocytes was 49.9% at the beginning; it was increased significantly to 61.52% on day 15 (p=0.001). CONCLUSION: Oral beta glucan administration seems to stimulate proliferation and activation of peripheral blood monocytes in vivo in patients with advanced breast cancer.

Extrapleural hematoma as an unexpected finding on a follow-up chest X-ray after coronary surgery.

We present two cases of an extrapleural hematoma, on a follow-up chest X-ray after coronary artery bypass surgery using an internal mammary artery (IMA). In both cases, the finding was disclosed on a routine chest film obtained 1 month post-operatively, in a patient who was either asymptomatic or had nonspecific symptoms. Follow-up chest films showed spontaneous resolution in both patients. We emphasize the recognition and significance of such a self-limited post-operative radiological finding.

[Cortical blindness following coronary angiography].

Cortical blindness has been occasionally reported as a complication after cerebral angiography, but is rare after coronary angiography. The contrast agent is believed to be responsible for the sudden development of blindness. Although the exact mechanism is unknown, it appears that the contrast agent disrupts the blood brain barrier, mostly in the occipital areas. We report a 77-year-old man who suddenly developed transient, bilateral cortical blindness 4 hours after coronary angiography. Using contrast enhancement, the CT scan showed typical, symmetrical involvement of both occipital lobes. There were no other neurological deficits. Vision and CT findings returned to normal within 48 hours.

"Multi-enzyme-targeted" immunochemotherapy: a salvage therapy protocol.

Human tumor cells have markedly elevated activity of enzymes of the purine and pyrimidine de novo and salvage pathways. Our therapy protocol is based on these findings. Different antimetabolites (MTX, 5-FU, dFdC, AZT) were administered to hit key enzymes. Vindesine and ifosfamide were aimed to block macromolecules. Repair mechanisms were impaired by hydroxyurea and topotecan. DNA transcription was blocked by actinomycin. IFNs (alpha, gamma) and IL-2 served as immuno-modulators. 47 patients (age 61.5 years, Karnowsky score 85%) were treated in an out-patient-setting. Median number of cycles was 3. General toxicity was low. Leucocytes, platelets, and monocytes were significantly reduced during therapy, but returned to normal on day 29. Lymphocyte subtypes did not show significant changes. 3 complete clinical responses, 22 partial responses, 9 progressive diseases were observed. CR occurred in 1/4 patients with kidney, in 1/1 with bladder, and in 1/5 with breast cancer.

Transient bradycardia induced by carotid sinus pressure increases outflow obstruction in hypertrophic obstructive cardiomyopathy but not in valvular aortic stenosis.

BACKGROUND: The murmur of hypertrophic obstructive cardiomyopathy (HOCM) increases in intensity in about 80% of those patients in whom carotid sinus pressure (CSP) slows the heart rate. This does not occur in valvular aortic stenosis (AS). STUDY OBJECTIVES, DESIGN, AND PATIENTS: It was hypothesized that left ventricular (LV) obstruction increases with CSP in HOCM and not in AS. Furthermore, it was not clear whether it was the sudden bradycardia or CSP itself that was responsible for the effect noted. Therefore, studies were performed using two different interventions: (1) Doppler echocardiography was performed before and during CSP in 36 HOCM patients and 21 AS patients; (2) two patients with DDD pacemakers and HOCM were examined before and after pacemaker rate slowing. Finally, atrial pacing was performed in three HOCM patients at catheterization, and atrial pacing was either slowed or stopped (without CSP). RESULTS: LV outflow velocity and pressure gradient increased in 28 of 30 HOCM patients (92%) in whom heart rate decreased with CSP. The peak instantaneous pressure gradient increased from 45+/-37 to 77+/-53 mm Hg (p<0.005), and the velocity contour became more typical of HOCM. The pressure gradient increased from 30 mm Hg to 64 and 81 mm Hg, respectively, in the two patients with DDD pacemakers after pacemaker rate slowing. Similar results were seen with slowing or cessation of atrial pacing at catheterization. In contrast, the pressure gradient increased in only three of 21 AS patients (14%), to 44+/-28 from 41+/-25 mm Hg, and remained unchanged in the other 18. CONCLUSION: This study shows that LV outflow velocity and pressure gradient increase markedly in most HOCM patients (92%) if CSP succeeds in slowing the heart rate, but not in patients with valvular AS. A similar effect is obtained by simply decreasing the atrial rate in patients with DDD or atrial pacemakers. This increase in outflow tract obstruction is sufficient to account for the increase in murmur intensity. Decreased afterload (secondary to greater aortic decompression with the longer diastole), increased intrinsic force of contraction with the bradycardia (the Woodworth effect), and Starling's law may play independent roles in the dynamic increase in obstruction observed during CSP in patients with HOCM. Worsening of mitral regurgitation was not clearly shown to contribute to the increase in murmur, but it cannot readily be ruled out.

[Neo-adjuvants, adjuvants and palliative therapy for gastric carcinoma]. / Neoadjuvante, adjuvante und palliative Therapie des Magenkarzinoms.

Patients with gastric cancer have a poor prognosis. Because curative surgery is often impossible (metastatic disease) or extremely difficult (locally advanced tumors), and the majority of patients undergoing curative resection relapse, chemotherapy has been actively studied in gastric cancer. Several combination chemotherapy regimens have been developed with high activity in locally advanced and metastatic disease. Among them are 5-fluorouracil (5-FU) plus high dose methotrexate plus doxorubicin (FAMTX). It represents the reference treatment in many clinical trials. Recent schedules like etoposid plus cisplatin (EAP); etoposid plus leucovorin plus 5-FU (ELF) and epirubicin plus cisplatin plus 5-FU (ECF) show encouraging response rates, their toxicity is considerable, however. Randomized trials comparing chemotherapy with best supportive care showed an increase in overall survival and in quality-of-life. Up to now adjuvant chemotherapy has failed to improve survival as compared with surgical controls. Only half of the patients with locally advanced gastric cancer (LAGC) undergo macroscopic and microscopic tumor-free resection. Preoperative chemotherapy has shown very promising results even in patients who had primarily unresectable tumors. Approximately half undergo R0 resection after downstaging induced by active chemotherapy and the long-term survival rises to about 20%. There are hopes that the newest regimes may do this: new cytostatic drugs and the immuno-chemical approach to combine cytostatic drugs with cytokines will be of great importance.

New Q waves do not always a new infarct spell: right bundle branch block-dependent Q waves simulating infarct extension.

We present the electrocardiograms of three patients, representative of 14, with acute anterior wall infarction in whom, in contrast to current understanding, the appearance of right bundle branch block was associated with a shift of the initial vector of depolarization that resulted in 'new' Q waves in V1-V2 that mimicked extension of necrosis. This little-known electrocardiographic phenomenon should be kept in mind when consideration is given to attempts at reperfusion.

Balloon aortic valvuloplasty in the elderly: useful when there is no alternative.

Of 63 elderly patients with calcific aortic stenosis in whom balloon aortic valvuloplasty was performed, 26 treated with the new technique of Cribier and Letac are the subject of this report. Patients were referred for the procedure because they were at high surgical risk, or were not candidates for surgery. Seven matched patients who fit the criteria for balloon valvuloplasty but refused the valvuloplasty procedure served as controls. Aortic gradient decreased from 78 +/- 27 mm Hg to 35 +/- 20 mm Hg and aortic valve area increased from 0.47 +/- 0.16 cm2 to 0.83 +/- 0.38 cm2 (P < 0.0001). Symptomatic improvement was immediately obtained in each patient. Complications were rare, with only one patient needing vascular repair for femoral artery occlusion. Three patients died during the initial hospitalization (none during the procedure). Valvuloplasty patients were followed for a mean period of 9.6 +/- 9.4 months. Three months survival was 87%, 6 months survival was 76%, and 12 months survival was 61%. Four of seven patients in the control group (57%) died within 3 months after initial referral. Balloon aortic valvuloplasty is a useful treatment in elderly patients who are poor surgical candidates. It may have a positive influence on short-term survival.

Pronus angina (angina pectoris induced by stooping or crouching). A proposed mechanism.

Patients with severe coronary artery disease (CAD) sometimes complain of chest pressure upon crouching or bending-forward (pronus angina). The factors that trigger pronus angina are not clear. We therefore investigated 28 patients with CAD and 26 normal subjects in the sitting, knee-chest, stooping, and squatting positions. Systolic and diastolic blood pressures were found to increase by 13.5 and 19.5 percent (p < 0.005) in the stooping position. In addition, left ventricular (LV) ejection time index (LVETI) also increased (p < 0.005). Despite the acute rise in aortic pressure, which is expected to lengthen the pre-ejection period index (PEPI), the latter shortened slightly in 10 of 14 (71 percent) patients tested, suggesting augmentation in contractile force during the isovolumic phase. Finally, left atrial size increased (p < 0.005) during the knee-chest maneuver, suggesting that the LV size also increases upon bending forward. The effect of stooping on blood pressure was similar in magnitude to that of squatting. It is concluded that the triggering factor for "pronus angina" in severe CAD may be explained as a combination of hemodynamic events which acutely increase myocardial oxygen requirements.

The effect of venous occlusion with tourniquets on peripheral blood pooling and ventricular function.

Rotating tourniquets were once part of the traditional treatment of acute pulmonary edema. Their effectiveness has been questioned and vasodilator therapy has replaced them, but early favorable results suggested that they may play a beneficial role. A radioisotope technique was used to evaluate blood volume increments in the leg after venous occlusion at 60 mm Hg in 26 patients with left ventricular dysfunction following myocardial infarction. Mean radionuclide counts (reflecting the blood volume distal to the occlusion) increased from the preocclusion value. Thus, satisfactory trapping of blood is achieved. However, mean left ventricular ejection fraction (EF) decreased slightly but significantly and this decrease in EF was observed in 18 of 26 patients. Left ventricular end-diastolic and end-systolic volume equivalents tended to decrease slightly but not in all patients. Mean stroke volume and cardiac output equivalents were reduced by 14 percent while peripheral resistance increased significantly. The present study thus fails to support the hypothesis that preload reduction by tourniquets improves left ventricular function; the exact opposite effect may occur because of increased afterload.

Effects of the dipyridamole test on left ventricular function in coronary artery disease.

The dipyridamole stress test is used with thallium-201 to detect areas of inhomogeneity of blood flow that point to coronary artery disease (CAD). It is unclear whether dipyridamole produces inhomogeneous perfusion only or whether it actually decreases net flow in the obstructed vessels and produces true ischemia. It is also unclear what effect dipyridamole has on global and segmental left ventricular function. Therefore, ejection fraction, segmental wall motion and ventricular volume equivalents were measured before and after dipyridamole in 113 patients and 32 normal subjects. Ejection fraction responded in an abnormal fashion in 98 patients (87%), decreasing from 49 +/- 11% to 43 +/- 13% (p less than 0.0001), whereas it increased in 29 normal subjects (90%) from 57 +/- 6% to 64 +/- 10% (p less than 0.0001). Wall motion worsened distinctly in 75 patients (66%), and pressure/volume ratio deteriorated in 72%. The effect of dipyridamole lasted between 10 and 25 minutes, but was promptly reversed by aminophylline. These findings indicate that dipyridamole generally induces true ischemia in CAD. Furthermore, the degree of dysfunction is related to the angiographically assessed severity of CAD. The shortness of breath (seen in 10% of patients) may be partially explained by the findings, and it seems advisable to give aminophylline to every patient in order to promptly correct left ventricular dysfunction.

Color Doppler echocardiography of isolated cleft mitral valve. Roles of the cleft and the accessory chordae.

To study the mechanism of altered mitral function in the presence of an isolated cleft mitral valve (ICMV) with regard to the relative roles of the cleft and of the accessory chordae, seven patients with ICMV were studied with color Doppler echocardiography. Mitral insufficiency ranging from mild to severe was demonstrated in six cases. The regurgitant jet originated in each case from the site of the cleft: in five patients the regurgitant jet had a narrow base originating exactly from the cleft; in the sixth patient, the regurgitant flow presented as a broad-based jet suggesting that accessory chordae restricted the motion of the anterior mitral leaflet. Turbulent flow in the left ventricular outflow tract, starting at the level of the accessory chordae, was found in one patient in whom a pressure drop of 44 mm Hg was detected with continuous-wave Doppler imaging. The altered function of the mitral valve cleft stems from two elements, the cleft itself and the accessory chordae. Color Doppler flow imaging showed that the cleft was the main factor causing mitral insufficiency. The accessory chordae played an additional pathogenetic role in two patients by causing restricted mitral motion or left ventricular outflow tract obstruction.