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The purposes of this study were to test the pharmacokinetics and renal and otologic tolerances of a once-daily regimen of netilmicin and teicoplanin administered intramuscularly, alone or in combination (4.5 and 6 mg/kg, respectively), for 7 days in 30 healthy male volunteers. Teicoplanin induced only a mild increase in enzymuria. Nephrotoxicity was moderate and reversible with netilmicin; there was increased enzymuria and alteration in diluting ability, without significant changes in urinary beta 2-microglobulin levels, concentrating ability, and glomerular filtration rate. Ototoxicity was not detected in any of the subjects. Our results suggest that (1) teicoplanin and netilmicin given once daily induced only slight, reversible tubular damage, without any sign of ototoxicity; (2) their combination was not more toxic; and (3) clinical studies can be envisaged to evaluate the efficacy and tolerance of once-daily regimens in long-term treatment.

The authors are defining the significance of a metastatic neck node from an occult carcinoma and review all the necessary investigations including surgical neck exploration and frozen section to establish the diagnosis. In such a case a radical neck dissection is carried out without delay and postoperative radiotherapy is applied on the neck with special portals focused on the pharyngo-larynx area where any possible infraclinic tumor might be located. The occult primary may become clinically detectable after a variable time interval, this occurrence is rather rare and becomes exceptional when irradiation has been delivered on the neck after surgical exploration. A high incidence of distant metastases is noticed during the follow-up period. The long term prognosis of metastatic cervical lymph node is rather poor and depends in particular of the size of the involved node.

The acute effects of diltiazem on coronary reactive hyperemia were studied in 12 patients with flow-limiting coronary stenosis. Reactive hyperemia was elicited by injection of 8 ml contrast medium into the left coronary artery, while coronary sinus blood flow and left ventricular and aortic pressures were continuously recorded. Relative magnitude of hyperemia was estimated by the ratio of coronary flow at peak hyperemia to baseline flow (hyperemic ratio). Coronary resistance was calculated as the ratio between mean aortic pressure minus left ventricular mean diastolic pressure and coronary sinus blood flow. The 12 patients studied had flow-limiting coronary stenosis since their hyperemic ratio was significantly restrained when compared to that of seven control subjects (1.45 +/- 0.17 vs 2.02 +/- 0.24, respectively; p less than 0.001). The intravenous infusion of diltiazem (0.30 mg X kg-1) reduced heart rate, mean aortic pressure, and myocardial oxygen consumption (all p less than 0.001). After diltiazem the hyperemic ratio was blunted when compared to the basal state (1.36 +/- 0.15 vs 1.45 +/- 0.17, respectively; p less than 0.05), and hyperemia volume was reduced (-33%; p less than 0.001). The decrease in coronary resistance at peak hyperemia was also reduced from -30 +/- 8% to -25 +/- 8% (p less than 0.05). We conclude that diltiazem blunts coronary reactive hyperemia in patients with demonstrated flow-limiting coronary stenosis. This reduction of coronary flow response to a hyperemic stimulus could favorably influence blood flow distribution in patients with significant coronary stenosis.

A second generation analyser for potentiometric measurement of ionized calcium and pH (ICA2 Radiometer, Copenhagen) was tested with respect to analytical performance in two different laboratories. Newly-developed aqueous buffered solutions were used at different Ca2+ concentrations as well as biological specimens prepared from human subjects. The overall precision of ICA2 was very good: CV = 0.0-0.4% for within-run and 0.4-1.7% for day-to-day precision with protein-free solutions and CV = 0.3-0.9% for within-run precision on biological specimens. The adjusted value of Ca2+ to pH 7.40 is an analytical advantage for which the calculation is correct but the assumption made for this algorithm may limit its clinical relevance. Measurements were comparable on ICA2 when performed on either whole blood, serum or plasma. Pre-analytical conditions should be observed such as the choice of anticoagulant and anaerobic conditions. Such a reliable and accurate instrument may promote the use of ionized calcium measurement in daily clinical practice.

We assessed coronary reserve, by measuring the increase in coronary sinus blood flow (CSBF) after intravenous administration of dipyridamole (0.14 mg/kg/minute for 4 minutes), in 7 patients with primary scleroderma myocardial disease (PSMD) and in 7 control subjects. Coronary reserve was greatly impaired in PSMD: before administration of dipyridamole, CSBF was similar in patients with PSMD (89 +/- 32 ml/minute/100 gm, mean +/- SD) and in controls (100 +/- 15 ml/minute/100 gm); after dipyridamole infusion, CSBF was significantly lower in patients with PSMD (191 +/- 45 ml/minute/100 gm) than in controls (399 +/- 58 ml/minute/100 gm) (P less than 0.01). Six of the 7 patients with PSMD had angiographically normal epicardial coronary arteries and normal left ventricular function. Decreased coronary reserve may be an important contributor to the pathogenesis of primary scleroderma myocardial disease.

A 62-year-old man had circulatory failure from massive pulmonary embolism following a road accident. Despite intensive therapy including urokinase infusion, inotropic drugs, and mechanical ventilation, the patient's circulatory status deteriorated. When it became impossible to maintain the mean systemic arterial pressure above 50 mm. Hg and the cardiac index above 1 L. per minute per square meter, circulatory support by partial cardiopulmonary bypass with a membrane lung was begun. Acute circulatory failure and acute pulmonary hypertension were promptly reduced by this procedure, and patient's status necessitated only intravenous heparin infusion and mechanical ventilation. After 60 hours of bypass the patient was weaned from the membrane lung, and 1 month later he was discharged from the hospital.

The measurement of ionized calcium has evolved in the last decade, and can now be easily performed by clinical laboratories using direct potentiometric analyzers available from a number of manufacturers. An original protocol for a comparison of the analyzers was used through a parallel multicenter evaluation in France. Using newly developed aqueous buffered solutions, this study focused not only on the analytical performance and operational handling of analyzers, but also on possible interferences in biological samples and the clinical relevance of the measurement with respect to the techniques of sample collection. All the instruments exhibited good precision and linearity, and were easy to handle and robust for daily use. However, not all the models gave identical results on the same patient's specimen. The utility of some Ca2+ analyzers has been further enhanced by the ability to "correct" the results to pH 7.40, although care must be taken in the interpretation of these results. While there are a number of clear-cut situations in which Ca2+ measurement is more relevant than total calcium, it seems that chemical activity of Ca2+ in blood may sometimes be considered with great caution under pathological conditions. The role of Ca2+ measurement in routine will be discussed in relation to the potential benefits of the instruments in laboratories.

The authors performed 29 surgical interventions of this type (24 primary and 5 secondary implantations). The treatment protocols, especially, the radio-chemotherapeutic protocols, were not changed and the radiotherapeutic tolerance of these prosthetic implants was particularly outstanding. This method may find wide application as well after single total laryngectomy as after circular total pharyngeal laryngectomy with restoration by gastric transplant. Speech is generally produced as early as the 12th day and we may assert that it is much better than esophageal speech, the whole indications and results being considered. These are being discussed and sustained support by the therapeutic team appears to be necessary.

Coronary sinus blood flow (ml/100 g left ventricular [LV] mass/min) and coronary resistance (mean aortic minus LV mean diastolic pressures/coronary sinus blood flow, mm Hg/[ml/100 g/min]) were studied in 7 control patients and in 11 patients with severe dilated cardiomyopathy (DC) and normal coronary arteriograms. Basal coronary sinus blood flow was not different in the 2 groups. After intravenous administration of dipyridamole (0.14 mg/kg/min X 4 min), coronary sinus blood flow and dipyridamole/basal coronary sinus blood flow ratio were significantly (p less than 0.001) lower in the DC group than in the normal group (coronary sinus blood flow 188 +/- 48 vs 408 +/- 58, respectively; blood flow ratio 1.78 +/- 0.35 vs 4.01 +/- 0.56, respectively), and the coronary resistance was higher in the DC group than in the control group (0.39 +/- 0.15 vs 0.22 +/- 0.03, respectively, p less than 0.01). After administration of dipyridamole in patients with DC, no correlation could be found between coronary sinus blood flow and LV mean diastolic, mean aortic or coronary driving pressures, i.e., mean aortic minus LV mean diastolic pressures. Thus, in DC patients, neither an elevated LV diastolic pressure nor a low coronary perfusion pressure can totally account for the restriction of the coronary flow reserve after dipyridamole.

The acute effects of an intravenous infusion of bepridil (BEP) (4 mg . kg-1) on left ventricular (LV) hemodynamics, coronary sinus blood flow (CSBF), and myocardial metabolism were studied in eight patients with coronary artery disease. In contrast with data previously reported with calcium channel blockers, BEP induced an elevation in LV end-diastolic pressure from 12.0 +/- 7.1 to 20.1 +/- 7.2 mm Hg (mean +/- SD, p less than 0.001) and a fall in LV dp/dt max from 1339 +/- 302 to 1177 +/- 251 mm Hg . sec-1 (p less than 0.01). This significant alteration in LV function is likely to be explained by the lack of effect on heart rate and aortic pressure observed after an acute intravenous infusion of BEP. Myocardial oxygen consumption (MVO2) increased from 448 +/- 272 to 498 +/- 273 mumol . min-1/100 g LV (p less than 0.05) as did CSBF from 79.5 +/- 42.7 to 92.1 +/- 45.1 ml X min-1/100 g LV (p less than 0.01). Lactate extraction fell from 0.33 +/- 0.17 to 0.15 +/- 0.17 (p less than 0.05). A contrast medium-induced coronary reactive hyperemia (HPR) evidenced an increased hyperemic volume from 9.5 +/- 3.6 to 12.1 +/- 4.5 ml/100 g LV (p less than 0.01) and HPR duration from 23.3 +/- 6.9 to 32.3 +/- 15.4 sec (p less than 0.05) after BEP. However, the peak/resting CSBF ratio was blunted after BEP from 1.74 +/- 0.18 to 1.61 +/- 0.12 (p less than 0.05), evidencing a net effect of BEP on HPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular hypertrophy has been found to be associated with a reduction of coronary vascular reserve, which could be responsible for episodes of myocardial ischemia. To evaluate coronary flow and resistance reserve in patients with chronic aortic regurgitation, coronary sinus blood flow and coronary resistance were measured before and after an intravenous dipyridamole infusion (0.14 mg/kg per min X 4 min) in eight control subjects and eight patients with aortic regurgitation, exertional angina pectoris and normal coronary arteriograms. Coronary flow reserve, evaluated by the dipyridamole/basal coronary sinus blood flow ratio, and coronary resistance reserve, evaluated by the basal/dipyridamole coronary resistance ratio, were both significantly reduced in patients with aortic regurgitation (1.67 +/- 0.40 versus 4.03 +/- 0.52 in control subjects, p less than 0.001 and 1.71 +/- 0.50 versus 4.38 +/- 0.88 in control subjects, p less than 0.001, respectively). In patients with aortic regurgitation, basal coronary sinus blood flow was higher than in control subjects (276 +/- 81 versus 105 +/- 24 ml/min, respectively, p less than 0.001) and basal coronary resistance was lower (0.31 +/- 0.13 versus 0.95 +/- 0.17 mm Hg/ml per min, respectively, p less than 0.001), but coronary blood flow and resistance after dipyridamole were not significantly different in the two groups (461 +/- 159 versus 418 +/- 98 ml/min in control subjects, 0.19 +/- 0.11 versus 0.22 +/- 0.04 mm Hg/ml per min in control subjects, respectively). These data demonstrate that coronary reserve is severely reduced in patients with chronic aortic regurgitation and exertional angina.(ABSTRACT TRUNCATED AT 250 WORDS)