MDL 17,043 (MDL), a new cardiotonic agent, was given intravenously at a single dose of 0.5 mg/kg to 14 patients with congestive heart failure (stages II-III). The mean half-life of plasma elimination of the parent compound determined in eight subjects was 81 min. MDL is rapidly metabolized to the sulfoxide with a maximum plasma metabolite concentration reached at 15 min after parent drug infusion and a metabolite half-life of 164 min. In eight patients, the hemodynamic effects of MDL were compared with those of sodium nitroprusside (SN) given at a dose lowering mean blood pressure by 20 mm Hg. Both agents increased cardiac output (p less than 0.001 for MDL, p = 0.06 for SN) and decreased total peripheral resistance values (p less than 0.001 for both) and left ventricular end-diastolic pressure (wedge pressure) (p less than 0.001 for MDL, p less than 0.01 for SN). However, MDL was able to increase left ventricular stroke work, whereas SN failed. As both agents induced comparable changes in loading conditions, it can be assumed that MDL not only acts by peripheral vasodilation but also has a direct positive inotropic action on the heart muscle. Myocardial oxygen uptake, assessed indirectly by tension-time index, was not affected by MDL (p greater than 0.2) despite the improvement in myocardial contractile state, thus making this new agent suitable for the treatment of congestive heart failure secondary to ischemic heart disease.

Adult↗

PubMedDate not supplied

Acute hemodynamic effects of piroximone (MDL 19,205) in patients with moderate congestive heart failure: comparison with sodium nitroprusside.

Piroximone (MDL 19,205), a new imidazolone derivative, was given intravenously to 14 patients with congestive heart failure (NYHA class II-III), while under constant daily doses of digitalis and diuretics. In the first 3 patients, we determined the dose safely eliciting a favorable hemodynamic response. The subsequent 11 patients received 1 mg/kg of piroximone intravenously, and the hemodynamic effects were compared with those of sodium nitroprusside (SN) at a dose-lowering mean blood pressure by 10-20 mm Hg. Piroximone increased heart rate (13.2 +/- 2.0 beats/min, mean +/- SEM) and lowered mean arterial pressure (9 +/- 2.3 mm Hg). Both agents reduced similarly wedge pressure (6.5 +/- 2.9 and 9 +/- 2.9 mm Hg, respectively, for SN and piroximone) and total peripheral resistance. Cardiac index was increased less by SN (15%) than piroximone (48%) (p less than 0.001), and stroke work index significantly enhanced only by piroximone (p less than 0.001). The changes in loading conditions induced by the two agents being similar, it is likely that piroximone not only acts by peripheral vasodilation, but also possesses positive inotropic properties. Myocardial oxygen demand, assessed indirectly by tension-time index, was not affected by piroximone. Thus, piroximone appears to combine well-balanced vasodilator and inotropic properties which make this new agent potentially very useful for the management of congestive heart failure.

Adult↗

PubMedDate not supplied

Extended staging results from the detection of isolated tumor cells in the liver of colorectal cancer patients.

Liver metastasis, as well as local recurrence, are delineating factors of postoperative survival in patients suffering from colorectal cancer. We set up a PCR-RFLP assay to detect K-ras mutated cells in liver tissue as an indicator of possible isolated tumor cells (ITC) or micro-metastasis at the time of surgery. Sixty-four patients with K-ras codons 12 or 13 mutated colorectal cancer were clinically diagnosed for liver metastasis, as well as by PCR-RFLP assay of DNA from liver biopsies. Macro-metastasis was observed in the liver of 7 patients (11%), with no additional evidence of ITC. Likewise, in the liver of 14 patients (22%) only ITC, but no macro-metastasis was detected. In another 7 patients (11%) there was both, ITC and macro-metastasis. No macro-metastasis or ITC were found in 36 patients (56%). Thus, the PCR-RFLP assay added 14 cases (22%) with potential liver-metastasis to the 14 cases (22%) detected by clinical diagnostic means. T and N status were related to the refined detection and extended classification of liver involvement. We conclude that clinical and PCR-RFLP methods supplement each other and can increase the detection of cases with liver involvement, if applied together.

Adenocarcinoma↗

PubMedDate not supplied

[Changes in myocardial metabolism in patients with angina and normal coronary arteries].

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Adult↗

PubMedDate not supplied

[Traumatic ruptures of the diaphragma. Diagnostic and therapeutic problems (author's transl)].

Between 1970 and 1976, 34 cases of traumatic ruptures of the diaphragma were observed and treated at the Surgical Clinic of the University of Würzburg: 23 acute ruptures and 11 delayed diagnostic ruptures. The etiology and mechanism of the rupture are discussed. A predominency of left over right ruptures occured in 90% of cases. In only one case there was an open rupture of the right side. Among associated abdominal lesions, ruptures of the spleen are the most frequent. Among skeletal associated lesions, one observes most frequently, fractures of the ribs. In 4 acute cases, there were no herniated organs. In the 11 patients were diagnosis was delayed we always found herniated viscera. Symptoms and diagnostic means are discussed. Traumatic rupture of the diaphragm is an absolute surgical indication. In acute cases we attempt the repair through a laparotomy; delayed cases should be treated by thoracotomy. Among 23 cases operated in emergency, 3 died because of associated lesions. Operative mortality was zero in the 11 patients with delayed diagnosis.

Abdominal Injuries↗