Studies on the bioavailability of some new erythromycin esters.
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Biomedical subjects
Publications and source records attributed to D Alberti.
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To evaluate the effects of the chronic administration of the fixed combination slow-release, oxprenolol 160 mg and chlorthalidone 20 mg on left ventricular hypertrophy, ten hypertensive out-patients, with left ventricular hypertrophy documented by left ventricular mass index (LVMI) greater than 130 g/m2, were studied. After a two-week placebo period, patients were given the study medication, once daily for six months. Blood pressure and heart rate were measured, 24 h after-dosing, at the end of placebo and thereafter every month. A m-mode echocardiographic examination was performed at the end of the placebo period, after 1 month of active treatment and at the end of the study. In comparison with placebo, the study medication induced a significant reduction (p less than 0.01) of systolic and diastolic blood pressure, 24 h after dosing, after 1 month of treatment (from 181.0 +/- 18.5/108.5 +/- 12.0 to 146.5 +/- 10.8/94.0 +/- 7.7 mmHg), and this reduction was maintained until the end of the study (142.0 +/- 14.0/90.0 +/- 8.2 mmHg). At the 6th month and in comparison with placebo, a significant (p less than 0.01) reduction of left ventricular mass (LVM) and of LVMI was observed (LVM: from 295.9 +/- 113.8 to 221.5 +/- 66.1 g; LVMI: from 158.1 +/- 39.0 to 126.2 +/- 35.8 g/m2. In conclusion, our results confirm the good antihypertensive efficacy of the fixed combination slow-release oxprenolol and chlorthalidone and show that the study medication is able to induce a regression of left ventricular hypertrophy, in hypertensive patients.
A multicentre study, involving 358 subjects, was carried out to evaluate the effects of a low-Na/high-K dietary salt in hypertensive patients receiving beta-blocker monotherapy. At the end of a 4-week treatment period with 200 mg slow-release metoprolol patients were randomly divided into two groups: one group was given common salt and the other the dietary salt. Both salts were given at table, in double-blind conditions over a period of 4 weeks. The dietary salt group showed a systolic and diastolic blood pressure (BP) reduction (4.2 and 3.0 mmHg, respectively, in the supine position and 4.0 and 2.5 mmHg in the standing position), which was virtually absent in the common salt group. A statistically significant difference between the two groups was found only between the systolic values (P less than 0.05). Twenty-four-hour urinary sodium excretion did not change in either group, while the excretion of 24-h urinary potassium increased significantly in the dietary salt group. It is concluded that in mild or moderately hypertensive patients already receiving a beta-blocker, ancillary treatment with a low-Na/high-K salt can be expected to lead to a further, slight reduction in systolic BP, probably due to the daily potassium load (around 20 mmol).
The Authors report a case of a 49 year old female patient with Gardner's Syndrome and adenocarcinoma of the Ampulla of Vater. In this case, adenocarcinoma of the Ampulla of Vater was associated with duodenal polyp (adenoma), which suggests that adenocarcinoma is the consequence of malignant of duodenal polyps. The world medical literature was reviewed and 29 cases of periampullary carcinoma complicating familial polyposis or Gardner's Syndrome were analyzed.
Acodazole (NSC 305884) is a synthetic imidazoquinoline which has antimicrobial as well as antineoplastic properties. A Phase I trial of acodazole administered as a 1-h i.v. infusion once weekly X 4 was conducted. Mild to moderate nausea and vomiting and moderate burning and erythema at the infusion site were the only toxicities seen among 33 patients treated over 51 courses at doses between 20 mg/m2/week and 888 mg/m2. The first patient treated at 1184 mg/m2 developed an irregular pulse and was found to have a prolonged cardiac output interval (Q-Ti) on electrocardiogram and polymorphic ventricular tachycardia ("torsades des pointes"). Careful study of five additional patients treated according to a modified schedule (340 mg/m2 week one, 500 mg/m2 week 2, 666 mg/m2 week 3, and 888 mg/m2 week 4) revealed 20% or greater Q-Ti prolongation after 20 of 27 treatments; Q-Ti prolongation had resolved 24-36 h after each infusion. Q-Ti prolongation occurred at all dose levels; no ventricular arrhythmias occurred. Acodazole was cleared with a long t1/2 (20.7 h) primarily by nonrenal mechanisms. No alterations in peak plasma levels or excretion were seen in the patients in whom Q-Ti prolongation was detected. No antitumor activity was seen. Further development of acodazole will require delineation of pharmacological means of surppressing this Q-Ti prolongation.
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Cisplatin (NSC 119875) and carboplatin (NSC 241240) are platinum (II) analogues with very different spectra of toxicity. Cisplatin dose is limited by nausea and vomiting, renal dysfunction, and dose-related peripheral neuropathy, whereas carboplatin is myelosuppressive. There are also clinical and laboratory data that suggest that these drugs may not be completely cross-resistant. Therefore, the following phase I trial of combination therapy with cisplatin and carboplatin was undertaken. Since carboplatin toxicity is enhanced in the presence of renal impairment, carboplatin excretion was also evaluated in selected patients at the maximum tolerated dose. Thirty-three patients received 50 mg/m2 cisplatin and doses of carboplatin between 160 mg/m2 and 400 mg/m2. Sequential 20-minute infusions of carboplatin and then cisplatin were able to be administered at the standard doses of carboplatin (320 and 400 mg/m2) with thrombocytopenia to the degree expected if carboplatin alone had been given. However, 280 mg/m2 carboplatin followed by 25 mg/m2 cisplatin/d X 3 caused unexpectedly severe thrombocytopenia in seven of eight patients (median platelet nadir 45,000/microL; range, 12 to 321,000/microL; nadir was less than 90,000 in seven of eight patients). In three patients treated with 280 mg/m2 carboplatin plus 25 mg/m2/d X 3 cisplatin, pharmacokinetics of carboplatin were compared during consecutive monthly cycles without and with cisplatin. Modestly increased areas under the curve (AUC) for carboplatin (15% and 35%) with cisplatin were seen in the two patients who experienced more pronounced platelet suppression with combination therapy. No other limiting or unusual toxicity was seen with this combination. Responses, primarily in "platinum responsive" tumors, were seen. The combination of cisplatin plus carboplatin is feasible and merits further study.
To assess the efficacy and tolerability of metoprolol (MET), 200 mg slow release (SR) q.d., and nifedipine (NIF), 20 mg SR b.i.d., 20 mildly to moderately hypertensive outpatients (14 men and 6 women; mean age 41.5 years, range 27-49 years) were studied. After being withdrawn from previous antihypertensive treatments, the patients were given single-blind placebo for 2 weeks and thereafter, in double-blind, randomized sequence, MET and NIF, both for 2 weeks. At the end of each period of the study, blood pressure (BP) was recorded for 24 h using a noninvasive ambulatory BP monitoring device (ICR System) with readings taken every 10 min (from 6 a.m. to 6 p.m.), 15 min (from 6 to 12 p.m.), and 20 min (from 12 p.m. to 6 a.m.). Five patients did not complete the study because of the occurrence of unwanted effects (one patient on MET and four patients on NIF). In the 15 patients who concluded the study both drugs significantly reduced (p less than 0.01), in comparison with placebo, systolic BP (SBP), mean arterial pressure (MAP), and diastolic BP (DBP) throughout the 24 h (MET: -16.9, -11.5, and -8.9 mm Hg; NIF: -12.7, -8.4, and -6.6 mm Hg, respectively). In comparison with NIF, SBP and MAP but not DBP were significantly reduced by MET (p less than 0.01 and p less than 0.05, respectively). We conclude that in our patient population MET was more effective and better tolerated than NIF. A possible explanation could be the relatively young age of the subjects we studied.
Au-195m is a radio-isotope with an ultra-short half-life with which multiple sequential evaluations of ventricular function can be made. In order to evaluate the reliability and reproducibility of analyses of overall and regional ventricular function by radio-isotope ventriculography with Au-195m we studied 10 healthy volunteers and 12 patients with coronary artery disease. Each subject underwent 4 first-pass studies: 1 with Tc-99m and, 10 minutes later, 3 with Au-195m (2 basal studies separated by 3-5 minutes interval and, 10 minutes later, 1 after s.l. nitroglycerin administration). Regional wall motion was analyzed and ejection fraction and peak count rate were determined in each test. Our study showed that the ejection fraction obtained with Au-195m was reproducible (r = 0.98) and correlated well with the ejection fraction determined by using Tc-99m (r = 0.98). The values of the peak count rate obtained with Tc-99m were higher than those obtained with Au-195m. Due to the specially designed collimator and the technical characteristics of the gamma-camera we used, we were able to record sufficiently high count-rates to evaluate regional wall motion, and this analysis was also found to be reliable and reproducible. After s.l. nitroglycerin administration, normal volunteers showed a significant increase of ejection fraction in comparison with basal acquisitions (p less than 0.05), while a wide range of responses was observed in the group of patients with coronary artery disease. We conclude that radio-isotope ventriculography with Au-195m is reliable and reproducible and could be a valid method of monitoring rapid variations induced in overall and regional left ventricular function.
A sequence of RAO first-pass studies (first with 99mTc and then twice with 195mAu) was performed in 18 normal volunteers and in 12 CAD patients using two different types of collimator for medium energy: a standard collimator (MEMS) and a special high-sensitivity collimator (MEHS). The following data were compared: the peak count rate, the net LV end-diastolic counts and the LVEF. Using MEMS the end-diastolic counts acquired were so low (12% of 99mTc average value) that EF standard deviation had a mean value of 0.061 (range 0.045-0.081). With MEHS the following results were obtained: 1. the peak count rate and LV net end-diastolic counts with 195mAu were 55% and 50% respectively, of 99mTc values; 2. a good correlation was shown between LVEF values either with 99mTc and 195mAu (r = .97), or with 195mAu sequential studies (r = .98).
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Observation of three cases of rare thyroid pathology (medullary carcinoma, thyroid lymphoma, De Quervain's subacute thyroiditis) triggers a discussion of the need to take due account of such rare pathologies in preoperative differential diagnosis in order to avoid giving the wrong treatment. The fact that extemporary histological examination is no help in such situations is also discussed.
A case of unilateral pulmonary oedema (UPO) caused by rapid re-expansion after drainage of a spontaneous pneumothorax is reported. If acute respiratory failure is noted at the moment of re-expansion the condition can be brought within safe limits by careful clinical observation and if necessary the use of assisted respiration.
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Preliminary experience with the combined use of 24 pH-metering and Holter ECG monitoring in the differential diagnosis of angina-like-pain (ALP) is reported. Twenty patients aged 24-65 (15 females and 5 males) all with angina-like-pain were studied. The aim of the study was to differentiate between oesophageal and cardiac causes of the various types of chest pain and to investigate the possibility of their coexistence. 50% of the ALP patients with a negative non-invasive cardiological report presented a pathological gastroesophageal reflux. In 5% of the cases simultaneous coronary insufficiency and pathological gastro-oesophageal reflux was noted. The importance of performing both Holter recordings and pH-metering before subjecting patients to coronarography is therefore emphasised.