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Biomedical subjects

H O Klein

Publications and source records attributed to H O Klein.

At least 37 records · Page 2Linked to original sources

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.

Adolescent↗

Combination of interferons and cytostatic drugs for treatment of advanced colorectal cancer.

Three phase I/II trials were performed in patients with metastatic colorectal cancer using immunochemotherapy--a combination of recombinant interferon beta and gamma with low doses of cytostatic drugs. The third regimen, consisting of a cytostatic component containing 5-fluorouracil plus carboplatin plus mitomycin C besides the interferons, produced a high remission rate of 47%: 14/30 patients responded. The tolerability of this protocol was good and it could be administered on an out-patient basis.

Adenocarcinoma↗

Sequential high-dose methotrexate and fluorouracil combined with doxorubicin--a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group.

In a prospective phase III multicenter trial, 213 patients with advanced measurable or nonmeasurable gastric cancer were randomized to receive methotrexate (MTX), fluorouracil (5-FU), and Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) (FAMTX) or 5-FU, Adriamycin, and mitomycin (FAM). The results show a significantly superior response rate (41% v 9% [P less than .0001]), and survival (median, 42 weeks v 29 weeks [P = .004]) for FAMTX. There was a cumulative thrombocytopenia in FAM and not in FAMTX. The FAMTX protocol should be the reference treatment in future clinical trials that seek to improve the therapeutic outcome in advanced gastric cancer.

Adult↗

[Effect of tourniquet occlusion on peripheral blood pooling and ventricular function].

Rotating tourniquets are traditionally part of the treatment of acute pulmonary edema. However, their effectiveness has been questioned. A radioisotope technique was therefore used to evaluate directly the increments in the blood volume of the leg after venous occlusion using a pressure of 60 mmHg in 26 patients with left ventricular (LV) dysfunction following myocardial infarction. The increment in mean radionuclide count at serial 15-second intervals (reflecting the blood volume in the leg distal to the occlusion) increased significantly from the pre-occlusion value by 46 +/- 26% (p less than 0.0005). Thus satisfactory trapping of blood is achieved even in LV failure. However, mean ejection fraction decreased slightly but significantly from 0.23 +/- 0.10 to 0.21 +/- 0.10 (p less than 0.05), a decrease observed in 18 of the 26 patients. LV 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% (p less than 0.0005), while calculated peripheral resistance increased significantly. The present study fails to support the hypothesis that preload reduction by tourniquets improves LV function.

Blood Volume↗

An EORTC gastrointestinal (GI) group randomized evaluation of the toxicity of sequential high dose methotrexate and 5-fluorouracil combined with adriamycin (FAMTX) vs 5-fluorouracil, adriamycin and mitomycin (FAM) in advanced gastric cancer.

Until now advanced gastric cancer has been generally treated with the FAM chemotherapy protocol. Due to the relatively low response rates with this protocol we decided to start a randomized prospective phase II trial comparing the FAM with the FAMTX protocol. The primary aim of our trial was to compare the toxicity in both protocols. The FAMTX protocol has been demonstrated to be fully comparable with the toxicity of the FAM protocol. The trial has been extended to a phase III study. With respect to response rates and survival times it is too early for evaluation.

Adult↗

The mechanism of the obstruction in calcific aortic stenosis with bicuspid valve: a reason for failure of balloon aortic valvuloplasty in the elderly.

Percutaneous aortic balloon valvuloplasty failed to relieve the obstruction in 2 elderly patients with calcific aortic stenosis. Intraoperative and pathologic examination showed bicuspid aortic valve with symmetric cusps, straight and fibrotic cusp edges and fractured calcific nodules of the aortic valve. Failure of balloon valvuloplasty in these patients, in spite of successful fractures of calcific nodules, was due to inability to influence the spring-like action of the thickened edges of the valve which represents a specific additional cause of obstruction in calcific bicuspid aortic valve of the elderly.

Aged↗

The paradox of sudden slowing of idioventricular rhythm during exercise in complete heart block: modulation of automatic focus, concealed reentry, or Wedensky inhibition?

As a rule, exercise enhances the rate of discharge of idioventricular rhythms in complete atrioventricular (AV) block. The opposite effect, a sudden drop in the rate of discharge with subsequent resetting of the firing rate, was observed in an 18-year-old boy with chronic complete AV block. Two mechanisms for this paradoxical response to exercise are proposed: (1) delay in discharge of the automatic pacemaker focus by successful penetration of electrotonic potentials from nonconducted P waves across the area of block in the AV conduction system and into the pacemaker focus; and (2) discharge of the pacemaker focus by concealed reentrant extrasystoles. Wedensky inhibition is ruled out because of the resetting of the firing rate.

Adolescent↗

Increased intensity of the murmur of hypertrophic obstructive cardiomyopathy with carotid sinus pressure.

In a prospective study murmurs increased in intensity with carotid sinus pressure in 18 of 26 patients with hypertrophic obstructive cardiomyopathy (HOCM) (sensitivity, 69.2 percent for the 26 patients, 85.7 percent for the 21 patients in whom heart rate and blood pressure decreased with carotid sinus pressure). On the other hand, the murmur remained constant or decreased in all but one of 104 patients with valvular aortic stenosis, mitral insufficiency, hypertrophic nonobstructive cardiomyopathy, and systolic murmurs of miscellaneous origins (specificity, 99 percent; positive predictive value, 94.7 percent). Catheterization, indirect arterial pressure tracings, and echocardiographic studies indicated that carotid sinus pressure-induced bradycardia was associated with increased left ventricular outflow tract obstruction. The carotid sinus pressure-induced increase in the murmur is probably multifactorial: decreased aortic pressure and impedance; increased contractility immediately on sudden slowing of heart rate; further increase in obstruction as the mitral valve systolic anterior movement is enhanced; and delayed vasodilatation maintaining the obstruction even after return of heart rate to precarotid sinus pressure values. An increase in a systolic murmur with carotid sinus pressure is characteristic of HOCM.

Aortic Valve Stenosis↗

Paroxysmal heart block triggered by sitting up: a usually undetected cause of cerebral ischemia.

Modest postural changes may trigger symptoms of cerebral ischemia, and these are usually attributed to "postural hypotension." The mere act of sitting up in bed induced paroxysmal atrioventricular block with symptoms sufficiently severe to warrant pacemaker implantation, without changes in blood pressure, in two patients. These cases illustrate an easily treatable mechanism for posturally induced cerebral ischemia that may completely escape clinical detection if not looked for.

Aged↗

Preclinical and early clinical trial with mafosfamide as immune modulator.

Low doses of cyclophosphamide (CPA) modulate immune responses and induce complete tumor regression and cures in mice. The mechanism of action is related to the development of a T-cell-dependent immune reaction. We started a trial with mafosfamide (MAF), the active metabolite of CPA and found that the response of Ehrlich ascites-tumor (EAT) cells in vivo to this compound is biphasic. The highest cure rate (70%) is obtained with a low i.p. dose of 7 mg/kg/d. Hematologic side effects were not observed. Arguments for an immune mechanism involved are that (1) mice treated with MAF showed a statistically significant increase in spleen weight compared with untreated controls, (2) after treatment large numbers of mononuclear cells appeared in the ascites, and (3) long-term surviving mice were resistant to further challenge with large inocula of EAT. We started a pilot trial in patients with metastasizing and advanced renal cell carcinoma - a disease which can be considered to be influenced by the immunologic response of the tumor host. The starting dose of MAF was 24 mg/m2/d administered i.v. Therapy was repeated at 14 days interval on an out-patient basis. Monitoring of mononuclear cells in the peripheral blood with monoclonal antibodies using a FACS IV were performed two times a week. There are eleven patients on study. Up to now, four out of them have been fully evaluated with respect to toxicity, immune modulation and tumor response. With respect to response to treatment, 2 patients had no change of disease, 1 patient had a mixed and 1 patient a partial response. No hematological or other toxicities could be observed. All patients showed an increase in monocytes/macrophages as well as NK-cells--clearly related to therapy.

Adjuvants, Immunologic↗