Validity of high-dose ranitidine treatment (300 mg b.i.d.) in clinical practice: an open study in 68 consecutive cases of severe peptic disease.

Ranitidine, at doses of 300 mg b.i.d., brings about a pronounced inhibition of both daytime and nocturnal acid secretion. The aim of the present open study, conducted in 68 patients with peptic lesions of the upper gastrointestinal tract, was to assess whether or not ranitidine at 300 mg b.i.d. for 4 weeks was capable of healing these lesions, which had failed to respond to treatment with H2-antagonists at standard doses, even when administered over fairly lengthy periods (greater than 8 weeks). The results obtained show that the 300 mg b.i.d. regimen yields a marked gain in terms of healing of lesions and relief of symptoms (achieved in roughly 80% of cases), accompanied by excellent tolerance. It is concluded that a double dose of ranitidine is clinically justified in particular cases.

Effect of L-carnitine on ethanol and acetate plasma levels after oral administration of ethanol in humans.

In a randomized double-blind, cross-over experiment, 0.5 g/kg of ethanol in the form of white wine and 3 g of L-carnitine by intravenous infusion were administered to 15 healthy volunteers. Ethanol and acetate plasma levels and the urine concentrations of acetylcarnitine were determined. Administration of ethanol induced a significant increase of both plasma ethanol and acetate, lasting 6-8 hr. The concomitant administration of carnitine resulted in a significant decrease of plasma acetate, whereas plasma ethanol levels remained unmodified. Urinary acetylcarnitine content significantly increased following administration of ethanol plus carnitine, but not when L-carnitine alone was administered. The resulting conclusion is that administered L-carnitine might trap excess acetyls derived both from free acetate, formed by ethanol oxidation, and from acetyl coenzyme A, accumulated as a result of the ethanol-induced decrease in the Krebs cycle flux.

Evaluation of the therapeutic efficacy of L-carnitine in congestive heart failure.

To evaluate the therapeutic efficacy of L-carnitine in elderly subjects suffering from heart failure, secondary to ischemic and/or hypertensive heart disease, 38 patients (22 men, 16 women) were studied, aged from 65 to 82 years. In addition to traditional therapy (digitalis, diuretics, antiarrhythmic agents) given in all cases, 21 patients received oral L-carnitine on the basis of a randomized protocol in 1-g doses twice daily for 45 days (the other 17 received placebo). In the group treated with L-carnitine, a distinct improvement was observed in both subjective and objective conditions; reduced heart rate, edema and dyspnea, increased diuresis and a marked reduction in daily digitalis consumption. L-carnitine treatment also induced a significant reduction in serum cholesterol and triglyceride levels. No adverse reactions attributable to L-carnitine administration were observed in any of the patients.

Effects of short-term treatment with coenzyme A or sulodexide on plasma lipids in patients with hypertriglyceridemia (type IV) or mixed hyperlipemia (type IIb).

Twenty-seven inpatients suffering from type II and IV dyslipidemia, randomly divided into two groups of 14 and 13 subjects, were treated with coenzyme A (2,000 Lipmann U daily) and sulodexide (300 Lipasemic U daily), respectively, in both cases administered intravenously for 20 days. The principial plasma lipid parameters (total and HDL-cholesterol, LDL-cholesterol in subjects with triglyceridemia less than 400 mg/dl, triglycerides, apoproteins and lipoproteins) were recorded before and after treatment. Tests on patients included an assessment, on a semiquantitative scale, of symptoms arising from modifications of blood flow to the various organs. Statistical analysis of data demonstrated that coenzyme A has a significant cholesterol-lowering action (with an increase in HDL-cholesterol) and a more pronounced hypotriglyceridemic effect in both types of dyslipidemia considered, results on both variables proving more satisfactory than with the control drug.

Ceftazidime in patients with severe Pseudomonas infections.

Forty patients suffering from severe Pseudomonas infections (13 urinary tract infections, 8 of which complicated, 16 cases of pneumonia, 3 cases of sepsis, 1 case of sepsis with osteomyelitis, 2 cases of osteomyelitis, 1 case of ophthalmitis, and 4 cases of peritonitis) were treated with ceftazidime (1-6 g/die). Most cases presented with severe underlying conditions associated with, or predisposing to, infection (surgical intervention, neoplasia, immunodepression, etc.). Both microbiological results (38 out of 43 strains eradicated) and clinical outcome (28 infections cured, 10 improved, and only 2 unchanged) proved highly satisfactory. The authors advocate the empirical use of ceftazidime as first-line single-drug therapy in severe hospital acquired infections in high-risk patients.

A double-blind controlled trial of ranitidine 300 mg nocte and ranitidine 150 mg b.i.d. in the short-term treatment of gastric ulcer.

A multi-center study was carried out to compare the healing rates of ranitidine 300 mg nocte and 150 mg b.i.d. in the short-term treatment of gastric ulcers and to assess the side-effect liability of ranitidine 300 mg given in a single daily dose. Forty-five outpatients suffering from endoscopically and bioptically proven uncomplicated benign gastric ulcer were selected for the study. The patients were treated, for 4 weeks, on the basis of a double-blind randomized design. An endoscopic examination was repeated within 4 days after the end of the treatments. The patients who did not demonstrate complete healing were treated for an additional 4-week period. Clinical controls were performed to evaluate symptoms, antacid consumption, compliance with trial tablet consumption; hematological and biochemical tests were also carried out at the end of the 4 and 8-week periods. No differences were observed between the healing rate induced by 300 mg nocte and 150 mg b.i.d., after 4 weeks of treatment (76% and 79% respectively) and after 8 weeks (100% in both groups). Similar results were obtained as far as symptoms, antacid consumption and compliance are concerned. Neither treatment regimen induced appreciable side-effects.

Nodular hyperplasia of Brunner's glands.

A clinical, endoscopic, and histological study of 206 cases of nodular hyperplasia of Brunner's glands was carried out. Firm nodules with a reddened surface due to hyperplastic Brunner's glands were limited mainly to the first part of the duodenum and affected almost exclusively male patients. Gastric acid secretion after pentagastrin stimulation was significantly increased compared to normal. In most cases, biopsies of the nodule center revealed spreading of Brunner's glands from within the lamina propria to the surface epithelium, whereas in biopsies performed between nodules, Brunner's glands were limited to the deeper part of the mucosa. Thirty-six nodules completely removed by diathermy were composed almost entirely of Brunner's glands. The frequent association with duodenal ulcer, chronic gastric erosions, and cobblestone pattern of the gastric body mucosa, as well as the significant hypersecretory state, suggest that hyperacidity plays a role in the pathogenesis of nodular hyperplasia of Brunner's glands.

The kinetics of cefuroxime in ascitic and pleural fluid.

Adequate drug concentration at the infection site is a very important objective of antibiotic therapy. In this study we investigated the pharmacokinetics of the new methoximine, cefuroxime, in peritoneal and pleural fluids in 16 patients. After a 1-g dosage of cefuroxime, its concentration reaches a peak in ascitic fluid within 4-5 h. With a 2-g dose the peak level is reached in 2-3 h. After 5 h, cefuroxime concentration in ascites exceeds that in serum. Cefuroxime diffuses readily into the peritoneal space, where high concentrations (8-10 mcg/ml) are maintained for at least 6 h. Data on the kinetics in pleural fluid also seem to show high antibiotic diffusion rates, even if concentrations are never as high as those in blood at the same time following 1 g i.v. These favorable kinetic properties are probably due to low serum protein binding and to slow renal excretion.

A comparative evaluation of endoscopic retrograde cholangiopancreatography and the secretin-cholecystokinin test in the diagnosis of chronic pancreatitis: a multicentre study in 124 patients.

A comparative evaluation of ERCP and the bicarbonate output 30 min after stimulation of the pancreas with secretin and cholecystokinin-pancreozymin, was carried out in 124 patients, of whom 65 were affected by proven chronic pancreatitis (PCP), and 59 by only suspected chronic pancreatitis (SCP). In PCP patients the false negative results were 14.7% and 21.5%, respectively. In 5 of the PCP patients with false negatives on ERCP and functional test a normal result of both the procedures was found. ERCP and bicarbonate output were found to be abnormal in 12% and 40%, respectively of 59 patients with SCP. In 30 SCP subjects both procedures gave a normal result, and only in two cases were results abnormal. A correct classification of the SCP patients with pathological bicarbonate secretion and normal ERCP seems quite impossible. The diagnostic usefulness of ERCP results is preeminent but the of carrying out both types of investigation together may give complementary information in the evaluation of pancreatic disorders.

Effect of exogenous gastrointestinal peptides containing the C-terminal tetrapeptide of gastrin on calcium, calcitonin and parathormone serum levels in man.

Gastrointestinal hormones containing the C-terminal tetrapeptide of gastrin are involved in calcium homeostasis. The aim of this study was to investigate: 1) the effect of a standard meal (schedule a) and of a duodenal infusion of 5% aminoacid solution (schedule b) on calcium, CT and PTH serum levels in man; 2) the behaviour of these parameters during I.V. infusions of pentagastrin (mcg 1.5/Kg-hour), sincalide (mcg 0.04/Kg-hour) and caerulein (ng 75/Kg-hour) (schedule c). In order to avoid any possible interference by endogenous secretin release, schedule c was performed in 5 patients previously submitted to total gastrectomy. Schedule a and b were studied in 5 healthy volunteers. After a standard meal a slight increase of CT and PTH was measured. Duodenal infusion of aminoacid was followed by hypocalcaemia and slight but constant rise of CT levels, without significant variations of circulating PTH. Pentagastrin, sincalide and caerulein induced a slight but significant hypocalcaemia and a rise of serum CT levels, together with a significant increase of serum PTH. These findings suggest that peptides containing the C-terminal tetrapeptide of gastrin directly affect calcium homeostasis in the absence of secretin release.

[Sulfobromophthalein clearance and survival of cirrhotics after an elective porto-systemic shunt]. / Clearance della bromosulfonftaleina (B.S.F.) e sopravvivenza dei cirrotici dopo uno shunt porto-sistemico di elezione.

Preoperative clearance of a single dose of BSP was assessed in 72 candidates for porto-systemic shunt in cirrhosis of the liver. Comparison between those who had died (24) and those who had survived (48) several years later showed statistically significant differences with regard to equivalent liver volume, first uncorrected exponential (Ki), absolute clearance, and 45' retention. A certain degree of differentiation could be made out among the survivors, whereas those who had died could not be distinguished from the series as a whole, nor could correlations be established with the length of survival. No practical advantage was displayed by the more complex, computer-processed parameters as opposed to those that were more immediately available.

An evaluation of bilirubin kinetics with respect to the diagnosis of Gilbert's syndrome.

1. The kinetics of the plasma disappearance of bilirubin (2 mg/kg intravenously) were studied in 106 patients with Gilbert's syndrome and in 13 normal subjects. 2. All patients had significant decreases in hepatic bilirubin clearance and transfer rates from plasma to liver, resulting in increased values for plasma retention at 4 h. The calculated value for unconugated bilirubin production was normal in 40% of patients and increased in the remainder. 3. In 29 of the Gilbert's patients their bromosulphthalein kinetics were studied 1 week before the bilirubin test. These results were essentially normal and it was concluded that the hepatic clearance mechanisms for bilirubin and bromosulphthalein are different. 4. In 10 patients the bilirubin transport maximum (Tm) was found to be low whereas the relative storage capacity (S) was normal. Phenobarbitone treatment in four patients resulted in an increase in Tm, and S decreased in two patients and remained unchanged in the other two. 5. These results support the hypothesis that there are several variants of Gilbert's syndrome and that the bilirubin tolerance test is a useful diagnostic test.