Halobacteriovorax isolated from marine water of the Adriatic sea, Italy, as an effective predator of Vibrio parahaemolyticus, non-O1/O139 V. cholerae, V. vulnificus.

AIM: To detect marine Bdellovibrio and like organisms (BALOs) which are able to infect Vibrio parahaemolyticus from seawater of the Adriatic, Italy. To test, prey specificity and predation efficiency of our Halobacteriovorax isolate, named HBXCO1, towards 17 Vibrio and 7 non-Vibrio strains linked to the Adriatic sea, Italy. METHODS AND RESULTS: Double layer agar plating technique was used to enumerate BALOs and to evaluate their prey specificity and predation efficiency. Transmission electron microscopy and 16S rRNA analysis were used to identify them. Means of BALOs counts ranged from 5·0 PFU per ml (March 2017) to 98·6 PFU per ml (August 2016). HBXCO1 had the ability to attack all tested prey strains of V. parahaemolyticus, Vibrio cholerae non-O1/O139 and Vibrio vulnificus, but it did not prey on non-Vibrio strains and V. alginolyticus under the tested conditions. CONCLUSIONS: Bdellovibrio and like organisms capable of infecting pathogenic vibrios are naturally present in seawater of the Adriatic, Italy. Isolate HBXCO1 shows prey specificity preferentially for the Vibrio genus and high predatory efficiency towards a wide range of pathogenic strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The public impact of V. parahaemolyticus, non-O1/O139 V. cholerae and V. vulnificus in bivalves is relevant and current decontamination processes are not always effective. We believe that the predator HBXCO1 represents a potential candidate for the development of strategies of biocontrol of pathogenic vibrios in bivalves from harvesting to trade.

Multidrug-resistant and epidemic clones of Escherichia coli from natural beds of Venus clam.

Epidemic Escherichia coli clones have been recovered in marine sediment along the coast of Marche, an Adriatic region in central Italy. In the present study, E. coli strains from the clam Chamelea gallina, sampled from seven natural beds in the same area, were detected. Selected E. coli isolates from all sampling sites were screened for antimicrobial susceptibility, genetic diversity and correlation. The majority (60%) belonged to phylogroups A or B1, 31% to the other groups (B2, C, D, E, F), 8% to cryptic clades, and 1% were untypable. Moreover, 33.3% of isolates were resistant to at least one drug and 11% were multidrug resistant (MDR). The most common resistance was to tetracycline, ampicillin, and streptomycin. No clonality was detected, but the strains' high genetic heterogeneity pointed at multiple sources of microbiological contamination. MLST analysis found potentially pathogenic and even epidemic MDR strains in clams collected in class A (ST746 and ST46) and class B (ST393, ST58 and ST131) areas, indicating that strains of clinical origin are detectable in clams. These data highlight that eating raw or lightly cooked clams may pose a health risk if purification is not performed or is ineffective.

Cyclosporin A in marrow transplantation for leukemia and aplastic anemia.

A total of 29 consecutive patients with leukemia or aplastic anemia who received an HLA-identical marrow graft were given cyclosporin A (CyA) to prevent graft-versus-host disease (GvHD). These patients were compared with an historic group of 25 similar patients with leukemia or AA given methotrexate (MTX) for GvHD prophylaxis at this institution. Engraftment was faster in patients given CyA when compared with MTX patients, with less days of granulocytopenia (P = 0.04), a shorter interval before reaching a platelet count of 70 X 10(9)/l (P = 0.04), fewer major infections (P = 0.01), and fewer days on intravenous antibiotics (P = 0.02). There were no graft failures in CyA patients compared with four of 25 in MTX patients (P = 0.01). Early mortality was lower in CyA patients but not significantly (P = 0.06). The incidence of pulmonary complications was comparable, five of 29 and seven of 25 in CyA and MTX patients, respectively, but the clinical features of such complications differed. Interstitial pneumonia developing after day 30 was seen in MTX patients, whereas an acute respiratory distress syndrome developing between day +8 and day +18 was seen in CyA patients. Acute GvHD was less severe in CyA patients (P = 0.04), but chronic GvHD was comparable (P = 0.3). The actual one-year survival is currently 72% and 52% in CyA and MTX patients, respectively (P = 0.1). Although our initial experience with CyA is encouraging with regard to engraftment and acute GvHD, optimization of CyA protocols will probably be needed for it to be proven as having a definite advantage over MTX.

Prophylaxis of fatal pulmonary embolism in general surgery using low-molecular weight heparin Cy 216: a multicentre, double-blind, randomized, controlled, clinical trial versus placebo (STEP). STEP-Study Group.

The effectiveness of low-molecular weight heparin CY 216 in the prophylaxis of fatal pulmonary embolism in patients undergoing general surgery was assessed in a multicentre, double-blind, randomized, clinical trial against placebo. A total of 4,498 patients aged over 40 undergoing general surgery were enrolled in the 18 centres which took part in the trial. Patients received a single daily subcutaneous injection of 7,500 anti-Xa units I.C. of CY 216 or placebo two hours before surgery, 12 hours after the initial injection and then daily for at least seven days. A post-mortem examination had to be carried out in every patient who died. The two groups of patients were well-matched for age, sex, type of disease, site and duration of operation as well as for incidence of risk factors which could predispose to the development of thromboembolism. Twenty-six deaths were recorded and validated: eight (0.36%) in the CY 216 group and 18 (0.80%) in the placebo group (p less than 0.05). At the post-mortem examination, carried out in 23 patients (88.5%), two deaths were found to be directly due to pulmonary embolism (0.09%) in the CY 216 group and four (0.18%) in the placebo group. Pulmonary embolism contributed to death in four other placebo-treated patients. Pulmonary or extrapulmonary thromboembolism was a significantly less frequent direct cause of death (p less than 0.05) in the CY 216 group (two pulmonary embolisms) than in the placebo group (four pulmonary embolisms, one acute myocardial infarction, one disseminated intravascular coagulation, two ischemic cerebral strokes).(ABSTRACT TRUNCATED AT 250 WORDS)

[Dihydroergotoxine mesylate in the treatment of senile cerebral insufficiency. Result of a long-term multicenter double-blind clinical trial with a placebo]. / Le mésylate de dihydroergotoxine dans le traitement de l'insuffisance cérébrale sénile. Résultat d'une étude clinique multicentrique en double aveugle contre placebo à long terme.

Many controlled double-blind clinical trials against placebo and other drugs have clearly demonstrated the activity of dihydroergotoxine mesylate (DHT) on some symptoms of chronic senile cerebral insufficiency (CSCI). In spite of this, there is still some controversy about the usefulness of DHT for treatment of CSCI, as it seems to be hard to transpose the results of these studies to treatment of a population with DHT. Trying to overcome this criticism, a multicenter double-blind, placebo-controlled long-term (1 year) clinical trial has been planned, using very simple criteria for patient selection and easy to use assessment devices. Fifty two centres distributed throughout Italy were invited and 40 took active part in the study. The present report deals with data collected for analysis on Aug. 31, 1982. On this date 559 patients entered the study and 458 were under treatment (229 on DHT 1.5 mg t.i.d. and 229 on placebo). 101 patients dropped out (48 on DHT and 53 on placebo). 388 patients (195 on DHT and 193 on placebo) had completed 6 months and 204 (111 on DHT and 93 on placebo) had completed 1 year of treatment. The data from patients who completed 6 and 12 months of treatment period were analyzed statistically using Student t tests for paired and unpaired data, the large number of patients being adequate protection against any non normality in the distribution of the data. Differences with 2P values of 0.01 or less were considered significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Pirenzepine in peptic ulcer. Introduction to clinical trials reports.

The main pharmacodynamic characteristics of pirenzepine are briefly reported and the experimental plan of the clinical trial on pirenzepine in peptic ulcer is discussed.

Pirenzepine (LS 519) in severe duodenal ulcer and in gastric ulcer. A double-blind clinical trial.

Duodenal ulcer. Forty-five of 49 adult outpatients with active, severe, endoscopically proven duodenal ulcers completed a 4-week double-blind trial comparing two doses of LS 519 (75 and 150 mg/day) with placebo. After 2 weeks, 1 of 15 patients given LS 75 mg and 4 of 15 given LS 150 mg/day had healed (P = 0.09). No patient given placebo had healed. After 4 weeks, 6 of 15 (40%) on placebo, 9 of 15 (60%) on LS 75 mg and 13 of 15 (86.7%) on LS 153 mg had healed (P less than 0.01). Patients given the highest dose of LS had significantly more pain-free days and nights and took fewer antacid tablets than those receiving the lowest dose of LS or placebo. Gastric ulcer. 19 of 20 adult outpatients with endoscopically proven active benign gastric ulcers completed a double-blind 4-week trial with either LS 519 (75 mg/day) or carbenoxolone (300 mg/day). Six of 10 (60%) given LS and 6 of 9 (66.7%) given carbenoxolone had healed after 4 weeks (N.S.). Symptomatic improvement was significantly faster in the LS group than in the carbenoxolone group. Hypokaliemia, increases in alkaline phosphatase and SGOT were observed in the carbenoxolone group.

Pirenzepine in duodenal ulcer. A multicentre double-blind controlled clinical trial, First of two parts.

Eighty-four patients with endoscopically-proved active duodenal ulcer were admitted to a multicentre double-blind trial with either pirenzepine tablets (25 mg three times per day for 1 week followed by 25 mg two times per day for 3 weeks) or placebo. Seventy-nine patients completed the trial, 44 treated with pirenzepine and 35 with placebo. After 4 weeks, complete healing had been achieved in 52% of the pirenzepine-treated patients and in 34% of the placebo-treated ones. Symptomatic responses were signigicantly better in those receiving pirenzepine than in those receiving placebo. In addition, the supplementary antacid consumption was significantly lesser in the pirenzepine group than in the placebo group. No important side-effects were observed in the two groups.

Dose-response study of a new oral bronchodilator, NAB 365 (clenbuterol).

A new oral bronchodilator, NAB 365 (clenbuterol), at doses of 10, 20, 30 and 40 microgram, was studied in a double-blind placebo-controlled incomplete cross-over study in 10 patients suffering from chronic bronchitis who had reversible airway obstruction. The ventilatory response was assessed by measurement of the forced expiratory volume in 1 sec (FEV1), total airway resistance (Raw) and specific airway conductance (sGaw) before and 30, 60, 120, 180, 240, 360 and 480 min after administration. With the 30 and 40 microgram doses, a significant bronchodilating effect was seen between 30 and 360 min after administration, with peak effects between 120 and 240 min. The maximal effects in ventilatory response after 30 microg were only slightly less than after 40 microgram; the bronchodilating effect of 20 microgram was statistically less marked than those of 30 of 30 and 40 microgram on FEV1, but not statistically different on Raw and sGaw. These findings have been briefly discussed. The effects of 10 microgram and of the placebo were always statistically lower than those of 20 microgram. No significant cardiovascular effects and no subjective side effects were observed. In conclusion, the results suggest that 30 microgram of NAB 365 (clenbuterol) are the suitable acute dose.

Hypotensive action and side-effects of flutonidin in normal subjects. A double-blind controlled trial.

In a double blind study, planned as a 7 x 7 latin square, three oral doses of flutonidin (0.5, 1, 2 mg), of clonidine (0.0075, 0.150, 0.300 mg) and of a placebo were administered to 7 normal volunteers on 7 different treatment days, with an interval of 3 days. On each treatment day sitting blood pressure, heart rate and reaction time were measured, and sedation and dry mouth evaluated before the 1, 2, 3, 4, 6, and 8 h after administration. The placebo did not modify the basal value of any variable. Flutonidin and clonidine produced dose-related effects on blood pressure, heart rate, sedation and dry mouth, but did not influence reaction time. Analysis of the dose-response curves demonstrated that the effect of flutonidin was one-fifth to one-twelfth that of clonidine, depending on which variable was considered.

Comparison of effects of guanfacine and clonidine on blood pressure, heart rate, urinary catecholamines, and cyclic nucleotides during and after administration to patients with mild to moderate hypertension.

In a random trial, the effects of treatment and withdrawal of guanfacine were compared with those of clonidine in 20 uncomplicated hypertensive patients. Elevated blood pressure returned to normal or responded well in all the patients given either guanfacine once daily or clonidine thrice daily. The pulse rate was reduced comparably by both treatments after 12 weeks, but the effect of guanfacine developed more gradually. Both guanfacine and clonidine significantly inhibited urinary noradrenaline, dopamine, and cyclic nucleotide excretion, while urinary adrenaline levels were unaffected. Side effects occurred earlier during treatment with clonidine. After sudden withdrawal, all the parameters tended to increase gradually in the guanfacine group, reaching base line by days 4-6. In the clonidine group the increase was more rapid, with pretreatment values reached within the 2nd day, and sometimes these values were surpassed. After withdrawal of clonidine all the patients had one or more side effects, most of them occurring within 48 h, while only 60% of the patients in the guanfacine group reported the appearance of unwanted symptoms, on days 3-6. It is concluded that there are close similarities between the effects of guanfacine and clonidine on the parameters evaluated, except for dopamine excretion, which was significantly less affected by guanfacine. Marked differences were found after abrupt withdrawal, with guanfacine less likely to produce the "discontinuation syndrome," probably due to its long half-life.

Beta-blockers and psychic stress: a double-blind, placebo-controlled study of bopindolol vs lorazepam and butalbital in surgical patients.

One hundred patients scheduled for surgery participated in a randomized double-blind trial designed to evaluate the effects of acute treatment with two doses of bopindolol (1 mg:BP1;2 mg:BP2) in comparison with those of 2.5 mg lorazepam (LR), 75 mg butalbital (BT) and placebo (PL). Anxiety was evaluated by the STAI X1 questionnaire on the day before surgery, in the late afternoon (time 0: basal) and in the evening (time 1). At the same times patients were requested to play a game of manual skill called "Go Down". The next day, in the morning (time 2), the patients were given the same questionnaire and were asked a series of questions about their sleep and awakening. Mean anxiety scores were significantly increased over basal values at both time 1 and time 2 in the PL and LR groups and at time 2 in the BT group, but neither in the BP1 nor in the BP2 group. The time needed to perform the "Go Down" test was significantly shorter than the basal value for both BP groups and significantly longer for the BT group, while nonsignificant modifications occurred in the PL and LR groups. Positive effects were obtained in patients treated with BP, at both doses, on ease of "falling asleep", number of "night awakenings" and "reawakening mood" while LR and BT were mostly ineffective, except for BT on ease of "falling asleep". It was concluded that a beta-blocker such as bopindolol may be more effective than a benzodiazepine or a barbiturate for the prevention of anxiety symptoms induced by a clearly defined stress situation, such as awaiting a surgical operation.

Effects of pindolol and metoprolol on plasma lipids and lipoproteins.

1 The effects of two beta-adrenoceptor blocking drugs, pindolol and metoprolol, on plasma lipids and lipoproteins were studied in sixteen hypertensive patients (WHO I-I) by a cross-over design, with two active treatment periods of 12 weeks each. 2 Neither pindolol nor metoprolol had any effect on total plasma cholesterol (total-C), triglycerides (TG) or low-density lipoprotein cholesterol (LDL-C). 3 Pindolol significantly increased high-density lipoprotein cholesterol (HDL-C). After metoprolol, HDL-C levels remained similar to those in the placebo period. 4 The ratio of total-C to HDL-C was significantly reduced by pindolol only. 5 Compared with the placebo period, both pindolol and metoprolol significantly reduced heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure. The decreases in HR were significantly greater after metoprolol. No differences between the effects of the two drugs on SBP and/or DBP were observed.

A single blind comparison of dihydroergotoxine mesilate and clonidine for treatment of hypertensive emergencies.

The effectiveness and safety of dihydroergotoxine mesylate (DHT) and clonidine (CLO) as acute antihypertensive treatments were studied in a single-blind randomized controlled study of 28 patients hospitalized after abrupt increases in mean blood pressure (MAP) to more than 150 mmHg, with concomitant symptoms related to hypertensive status (16 patients). Intravenous infusion of 1.5 mg DHT significantly reduced both systolic (SBP) and diastolic (DBP) blood pressure from 227 +/- 2/128 +/- 2 mmHg to 160 +/- 4/94 +/- 2 mmHg by 1 hour after the onset of infusion (p less than 0.01). In patients given CLO, BP values fell from 221 +/- 3/123 +/- 3 mmHg to 166 +/- 5/95 +/- 3 mmHg after 150 minutes. After that BP values did not change significantly up to 6 hours after both treatments. One hour after the onset of infusion, mean heart-rate (HR) had decreased by 15 beats/min in the DHT group and by 10 beats/min in the CLO-group. Twenty-one per cent of the patients given DHT and 78% of the patients given CLO complained of mild or moderate side-effects. The results of this study showed that DHT is an effective and well tolerated agent for the treatment of hypertensive emergencies and can be used safely even when continuous monitoring of blood pressure cannot be carried out.