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Thrombolysis after acute myocardial infarction may lead to a number of adverse effects (reperfusion injury) such as myocardial stunning, arrhythmias and even myocardial damage and extension of the infarct size. Some recent clinical studies have demonstrated that the intravenous infusion of N-acetylcysteine during thrombolysis was associated with a decrease in infarct size and better preservation of left ventricular function, probably due to antioxidant and free radical scavenger properties of N-acetylcysteine. Short- and long-term studies indicated that also in patients with unstable angina pectoris and threat of infarct, the intravenous or oral administration of N-acetylcysteine in association with nitroglycerin is highly effective in decreasing the risk of worsening, mainly by preventing the occurrence of acute myocardial infarction.

Evaluation of arm work capacity after radical neck surgery. The aim of this paper is to describe an approach for the assessment of work capacity in patients who underwent radical neck surgery, including those treated with radiation therapy. Nine male patients, who underwent radical neck surgery 2 months before being referred to our Unit, participated in the study. In addition to manual muscle strength test, we performed the following functional evaluations: 0-100 Constant scale for shoulder function; maximal shoulder strength in adduction/abduction and intrarotation/extrarotation; instrumental. We measured maximal isokinetic strength (10 repetitions) with a computerized dynamometer (Lido WorkSET) set at 100 degrees/sec. During the rehabilitation phase, the patients' mechanical parameters, the perception of effort, pain or discomfort, and the range of movement were monitored while performing daily/occupational task individually chosen on the simulator (Lido WorkSET) under isotonic conditions. On this basis, patients were encouraged to return to levels of daily physical activities compatible with the individual tolerable work load. The second evaluation at 2 month confirmed that the integrated rehabilitation protocol successfully increased patients' capacities and "trust" in their physical capacity. According to the literature, the use of isokinetic and isotonic exercise programs appears to decrease shoulder rehabilitation time. In our experience an excellent compliance has been noted. One of the advantages of the method proposed is to provide quantitative reports of the functional capacity and therefore to facilitate return-to-work of patients who underwent radical neck surgery.

Cancer patients are now more often long-term survivors and their needs for returning to social and productive activities have become a primary focus of intervention. The purpose of the present study was to propose an objective evaluation test for predicting endurance capacity in breast cancer patients after surgery, in order to optimize return to work or previous daily activities, and for monitoring changes during rehabilitation. Twenty female patients (mean age: 44 +/- 5), who underwent radical breast surgery 2 months before being referred to our Unit, participated in the study. In addition to the measures of the circumferences in the arm-forearm and manual muscle strength test, we performed the following functional evaluations: 0-100 Constant scale for shoulder function; instrumental evaluation of daily/occupational upper limb activities (Lido WorkSET). We monitored the mechanical parameters, the perception of effort, pain or discomfort, and the range of movement while performing a 3-minute steady daily/occupational task chosen by the subject. Patients were asked to perform the 3-minute test at three different intensities ("moderate", "somewhat hard", "hard") until the perception of fatigue, pain or discomfort was rated > 3 on the 10 point Borg's scale. The 'power-duration' product (Watt x min) defined by the three tests (see Fig. 1) represented the individual tolerable work load, since subjective indicators of pain/discomfort remained within tolerable limits during the exertion. On this basis, patients were encouraged to return to levels of daily physical activities compatible with the individual tolerable work load. The second evaluation, although no statistical analysis was performed, confirmed that the "guided" daily activity in a 2-month period increased patients' capacities and "trust" in their physical capacity.

The aim of this study was to evaluate the bronchodilating activity and the tolerability of broxaterol (B, CAS 76596-57-1) given as drops by inhalation after single administration at different doses and after repeated administrations for 1 month. Two groups of 12 patients each were treated in a double-blind fashion and according to a within-subject design: one group with B at the single doses of 1.25 mg and 2.50 mg and with placebo (P), and the other with B at the dose of 0.75 mg and with P. A further group of 12 patients was treated in open fashion for 1 month with B at the dose of 1.25 mg 3 times a day. On each study day for the single doses and on the 1st and 30th days for the repeated doses, forced vital capacity (FVC), forced expiratory volume (FEV1), maximal middle expiratory flow (MMEF), heart rate (HR) and systolic and diastolic blood pressure (BP) were measured immediately before and 15, 30, 60, 120 and 240 min after the conclusion of the treatment. At the beginning and at the end of the 1-month treatment period, haematology and biochemistry were checked. After B 0.75 mg, 1.25 mg and 2.50 mg the values of spirometric variables proved significantly and dose-dependently higher than the basal values. The changes from baseline in lung function test values with B (all doses) were significantly greater than with P.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics and the relative bioavailability of a soluble granular form (sachets) of a pharmaceutical formulation containing ibuprofen (CAS 15687-27-1) and 1-arginine were investigated in healthy volunteers. Two granular dosage forms were evaluated, 200 and 400 mg, in comparison with the commercial equivalents (tablets). After the oral administration of both granular dosage forms, a quicker absorption and a significantly higher plasma bioavailability of ibuprofen in the first hour following the treatment than after tablets administration were observed. The mean values of peak plasma concentration (microgram/ml) were 26.1 and 56.4 after treatment with 200 and 400 mg sachets respectively vs. 16.3 and 43.0 after treatment with 200 and 400 mg tablets. The mean values of peak time were 16.9 and 24.4 min after treatment with 200 and 400 mg sachets respectively vs. 90.0 and 63.7 min after treatment with 200 and 400 mg tablets. The shortening in the absorption time and the increase in the plasma concentrations did not involve a quicker drug elimination nor cause any changes in the bioavailability (mean values of the relative bioavailability indexes of 0.98 for 200 mg dosage form and 1.02 for the 400 mg one). The analgesic activity of soluble ibuprofen 400 mg was compared with that of ibuprofen 400 mg tablets in patients with osteo-articular pain, according to a single dose, double-blind cross-over balanced design. The results showed that the soluble granular form is able to determine an analgesic effect significantly quicker and higher than that of tablets.

The bronchodilating activity and the ability of broxaterol transdermal patch to inhibit bronchial constriction in response to distilled water mist (UNH2O) inhalation were assessed. The study was performed in 10 asthmatic patients in clinical remission according to a placebo-controlled, double-blind, randomized crossover design. Test medications were broxaterol patch (size = 1.75 cm2; programmed delivery = 105 mcg/h) and a matched placebo patch. A spirometric examination was performed before patch application (at 8:30-9:00 a.m.) and 24 hours later. Immediately afterwards, the UNH2O inhalation test was made, consisting of 3 bronchial exposures lasting 30, 60 and 120 s respectively with 3-minute intervals between challenges. Immediately after each exposure, a spirometric examination and specific airway resistance measurements were made. The results obtained show that broxaterol patch exerts a statistically significant bronchodilating effect and has a better protective effect than placebo patch on UNH2O-induced bronchial constriction. The local tolerability of patches was very good. Slight tremors were observed in some subjects.

The aim of the study was to evaluate in man the dose-effect relationship of ibopamine solution 0.25%, 0.50% and 1% on the pupillary diameter and the pupillary reflex to light stimulus and near vision. A cross-over study was performed in comparison with a placebo and with tropicamide solution 1% in 18 healthy volunteers. The results show that ibopamine 1% determines a marked mydriatic effect. At the doses used, it produces a maximum increase of the pupillary diameter with a dose-effect relationship which does not depart significantly from a straight line. The maximum mydriatic effect of ibopamine 1% is significantly greater than that of tropicamide 1%. The mydriatic effect of ibopamine lasts for about 3 h; that of tropicamide lasts longer. Tropicamide 1% markedly and for a long period inhibits the pupillary reflex both to light and to near vision. The effect of ibopamine 1% on the pupillary reflex to near vision is slight, while on the reflex to light stimulus it is essentially comparable to that of tropicamide.

In order to describe kinetics after single administration and to test dose independence in the therapeutic dose range, ibopamine (SB-7505), the 3,4-diisobutyrylester of N-methyldopamine (epinine), was given orally to six healthy volunteers at multiple dose levels in a cross-over fashion. Doses employed were 50, 100 and 200 mg with a wash-out period of at least three days between doses. Plasma levels were studied after the 100 mg dose, and urinary recoveries of the major metabolites were measured after each dose. After oral intake of ibopamine, both conjugated and free epinine were detectable in plasma at the earliest sampling times (i.e. 5-10 min), with a hybrid absorption half-life of 0.25 h. Peak plasma concentration mean values of total and free epinine were 33 mumol/l and 35 nmol/l, respectively, and mean time to plasma peak concentration was 1.5 and 0.71 h, respectively. 24-h urinary recovery of conjugated epinine, homovanillic acid and dihydroxyphenylacetic acid accounted for about two thirds of the dose, without dose-dependent mechanisms affecting total elimination. Presystemic sulfate conjugation as a potentially saturable metabolic step at higher dose levels is discussed, although evidence was not found of its saturation in the studied dose range.

The analgesic effects of single oral doses of viminol (70 mg), of viminol (70 mg) combined with chlordiazepoxide (10 mg) and of chlordiazepoxide (10 mg) were compared in 41 outpatients with chronic pain mostly due to neoplasms. Alone, or combined with chlordiazepoxide, viminol proved significantly more effective than chlordiazepoxide; No difference in analgestic effect was observed between viminol combined with chlordiazepoxide and viminol alone. The use of self-administered questionnaires was found particularly convenient for study of analgesics in outpatients.

The pharmacokinetics of ibopamine was studied after single dose and after single and multiple dosing. The studies after single dose were conducted in normal subjects (NS) and in patients with congestive heart failure (CHF) of NYHA functional classes II, III and IV, in patients with chronic renal impairment (CRI), with hepatic cirrhosis (HC) and in elderly patients. Furthermore, ibopamine-quinidine pharmacokinetic interaction and the effects of food on plasma kinetics were evaluated in NS. The studies after single and multiple dosing were conducted in CHF patients. The effects were also studied of chronic oral ibopamine treatment on the pharmacokinetics of digoxin after chronic oral dosing and of treatment with digoxin on ibopamine pharmacokinetics. Ibopamine appears to be rapidly and extensively absorbed, quickly hydrolyzed to epinine and then excreted mainly through the kidneys either after being sulpho-conjugated or oxidized to homovanillic acid and 3,4-dihydroxyphenylacetic acid. Epinine is thought to be the therapeutically active moiety of the drug. In patients with CHF epinine pharmacokinetics does not depend on the NYHA functional class, and it falls within the same area as that in NS; the pharmacokinetics of epinine does not vary during the repeated administration of the drug for one month. In patients with CHF the pharmacokinetic data do not suggest the need to adjust the dose according to the NYHA functional class. In patients with CRI the pharmacokinetics of epinine does not vary with the degree of renal impairment. In HC patients AUC and Cmax of epinine seem to be higher than in NS; in these patients a higher amount of epinine is excreted into urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood concentrations and pharmacokinetic parameters of cimetidine were studied in 16 patients with liver cirrhosis and in 8 apparently healthy subjects. The drug was administered orally as a single dose of 200 mg. Four patients of both groups were treated with cimetidine orally and intravenously. No statistically significant difference was observed between pharmacokinetic parameters of cimetidine obtained from control subjects and those from patients with liver cirrhosis. The pharmacokinetic parameters of cimetidine in patients with liver cirrhosis did not significantly differ from those of normal patients even if separately calculated with respect to serum albumin and total serum bilirubin.

The analgesic activity of Viminol R2 was compared to that of Pentazocine and placebo in a double-blind, "between subjects" study involving 42 patients with postoperative pain randomly assigned to 3 groups of 14 patients each and treated with a single intravenous dose of Viminol R2 10 mg, Pentazocine 30 mg or placebo. Pain relief scores were recorded over a 2 h period after treatment. The analgesic activity of Viminol R2 and Pentazocine was significantly greater than that of placebo both in terms of time-course of action and frequency of classes of satisfactory analgesia. No statistically significant differences were found between Viminol R2 and Pentazocine. No side effects were observed in any patients treated with Viminol R2.

The plasma pharmacokinetics of oral acetylcysteine(N-acetylcysteine, NAC) after the administration of single 600 mg and repeated 200 mg doses and the relative bioavailability of the two regimens were studied in 12 adult subjects. On two different occasions in a cross-over, balanced fashion the subjects were administered orally either a single dose of NAC 600 mg as effervescent tablets or 4 repeated doses of NAC as granules in sachets at the regimen of 200 mg t.i.d. Venous blood samples were obtained just before dosing and 20, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h after the administration of NAC 600 mg; with the 1st, the 2nd and the 4th doses of NAC 200 mg samples were taken just before dosing and after 20, 40 min, 1, 1.5, 2, 3, 4, 6 and 8 h, the last sampling after the 1st dose being the one before the 2nd dose. A detailed description of the assaying methods of NAC is given in the text. As indexes of bioavailability Cmax' tmax and AUC of NAC plasma concentrations were considered and MRT was taken as an estimate of its persistence in plasma. NAC was quickly absorbed without any significant difference in tmax among the doses. With the 600 mg dose Cmax' AUC and MRT were greater than with a single 200 mg dose; after summing up the values of these parameters for the 200 mg doses no significant differences were observed in comparison to the single 600 mg dose in Cmax and AUC, while MRT resulted significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics of fosfomycin and trometamol after single oral dose of fosfomycin trometamol (Z 1282) was studied in healthy volunteers in fasting conditions and immediately after standard meal. The dose was of 1.876 g (equivalent to 1.0 g of fosfomycin). The parameters considered were: serum apparent elimination half-life (t1/2), maximum serum concentration (Cmax), time to Cmax (tmax), area under the curve of the serum concentrations from time 0 (zero) to infinity (AUC0-infinity) and urinary recovery in the first 48 h. The results confirm that fosfomycin trometamol allows high bioavailability of fosfomycin. The absorption and elimination rates of fosfomycin and trometamol in the serum were similar. A statistically significant difference was found between the Cmax values of fosfomycin in the 2 experimental conditions. Means +/- SE of Cmax (micrograms/ml) were 12.1 +/- 0.6 in fasting conditions and 7.8 +/- 1.6 after a meal. Urinary recovery of the antibiotic was high in both experimental conditions. The fraction of the dose recovered (the dose being taken as equal to 1) was on the average 0.58 in the first condition and 0.52 in the second. Urinary recoveries of trometamol in the 2 different conditions were similar.

The pharmacokinetics of ibopamine after single and multiple dosing was studied in 20 patients with congestive heart failure (CHF) of NYHA functional class II. Ibopamine 100 mg was given 3 times a day for 7 days in 6 patients and for 30 days in the other 14 patients. Plasma pharmacokinetics of total (mainly conjugated) and free epinine was studied after the first dose and on the 3rd, 7th and 30th days of treatment. The urinary recoveries of total epinine, HVA and DOPAC were measured in 5 patients for 24 h after ibopamine ingestion on the 1st and 30th days. Plasma pharmacokinetics of ibopamine did not vary during the repeated administration of the drug. In the course of the treatment, total epinine elimination t1/2 showed no significant variations. The build-up of Cmax, Cmin and AUC of total epinine observed after multiple dosing was as expected on the basis of the interval adopted between the doses of ibopamine and of the elimination t1/2 of total epinine. Pharmacokinetic parameters of free epinine did not show significant variations during the course of the treatment. The amounts of HVA and DOPAC recovered in urine on the 1st and 30th days of treatment were similar while the amount of total epinine was greater on the 30th day, the increment mainly reflecting a partial carry over of the less rapidly excreted conjugated epinine from the last previous doses. The results obtained for free epinine plasma levels and for the urinary recoveries of ibopamine metabolites thus indicated that no saturation of the enzymes involved in ibopamine metabolism occurred.

A group of patients was treated with stanozolol. A modified version of Roebuck's skin window technique was used to obtain macrophages. These were then fixed in vitro with a suspension of Paracolonbacter aerogenoides. Comparison with a group of control subjects showed that the macrophages from the treated patients appeared to take up and destroy germs more effectively and that this could be potentiated by prior opsonisation with serum from the treated subjects. These results are seen as an expression of functional activation of the macrophages and an increase in serum opsonin content.