Practice testing of generic quality indicators for responsible antibiotic use in nine hospitals in the Dutch-Belgian border area.

BACKGROUND: Inpatient quality indicators (IQIs) were previously developed to assess responsible antibiotic use. AIM: Practice testing of these QIs in the hospital setting. METHOD: This study was performed within a Dutch-Belgian border network of hospitals implementing the Infection Risk Scan (IRIS) point prevalence survey (PPS) as part of the i-4-1-Health project. Twenty out of 51 DRIVE-AB IQIs, including 13 structure and seven process IQIs, were tested. Data on structure IQIs were obtained through a web-based questionnaire sent to the hospital medical microbiologists. PPS data from October to December 2018 were used to calculate performance scores for the process QIs. FINDINGS: Nine hospitals participated. Regarding structure IQIs: the lowest performance scores were observed for recommendations for microbiological investigations in the guidelines and the use of an approval system for restricted antibiotics. In addition, most hospitals reported that some antibiotics were out of stock due to shortages. Regarding process IQIs: 697 systemic antibiotic prescriptions were used to calculate performance scores. The lowest score was observed for documentation of an antibiotic plan in the medical file (58.8%). Performance scores for IQIs on guideline compliance varied between 74.1% and 82.3% for different aspects of the antibiotic regimen (duration, choice, route, timing). CONCLUSION: This multicentre practice testing of IQIs identified improvement targets for stewardship efforts for both structure and process aspects of antibiotic care (approval system for restricted antibiotics, documentation of antibiotic plan). These results can guide the design of future PPS studies and a more extensive evaluation of the clinimetric properties of the IQIs.

Efficacy of ustekinumab in the treatment of patients with Crohn's disease with failure to previous conventional or biologic therapy: a prospective observational real-life study.

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

The potential diagnostic and predictive role of anaplastic lymphoma kinase (ALK) gene alterations in melanocytic tumors.

OBJECTIVE: Anaplastic lymphoma kinase (ALK) gene has been demonstrated to be rearranged, mutated or amplified in several haematological and solid tumors. Moreover, the use of ALK inhibitors has recently revolutionized the treatment of ALK-rearranged patients affected by non-small cell lung carcinoma. Herein we review the genetic alterations of ALK in melanocytic neoplasms described in literature, focusing on their potential diagnostic and predictive role. MATERIALS AND METHODS: The Authors reviewed the pertinent literature through research on PubMed server was performed typing the terms "ALK", "Anaplastic lymphoma kinase", "ALKATI", "Melanoma", "Spitz", "Spitzoid". RESULTS: ALK translocations were demonstrated in melanocytic neoplasms, particularly in acral melanoma and spitzoid tumors. ALKATI was described in primary and metastatic melanoma, indicating its early occurrence in oncogenesis, with varying immunohistochemical expression of the protein. CONCLUSIONS: The identification of the specific type of ALK mutations could be interesting for planning biologic therapy of melanoma patients. Further studies are needed to evaluate the possibility to introduce an ALK-targeted therapy in patients affected by malignant melanoma.

Association between coffee or tea drinking and Barrett's esophagus or esophagitis: an Italian study.

BACKGROUND/OBJECTIVES: Only a few papers have treated of the relationship between Barrett's esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We evaluated the role of these beverages in BE and E occurrence. SUBJECTS/METHODS: Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee and tea and other individual characteristics were collected using a structured questionnaire. RESULTS: BE risk was higher in former coffee drinkers, irrespective of levels of exposure (cup per day; ⩽1: OR=3.76, 95% CI 1.33-10.6; >1: OR=3.79, 95% CI 1.31-11.0; test for linear trend (TLT) P=0.006) and was higher with duration (>30 years: OR=4.18, 95% CI 1.43-12.3; TLT P=0.004) and for late quitters, respectively (⩽3 years from cessation: OR=5.95, 95% CI 2.19-16.2; TLT P<0.001). The risk of BE was also higher in subjects who started drinking coffee later (age >18 years: OR=6.10, 95% CI 2.15-17.3). No association was found in current drinkers, but for an increased risk of E in light drinkers (<1 cup per day OR =1.85, 95% CI 1.00-3.43).A discernible risk reduction of E (about 20%, not significant) and BE (about 30%, P<0.05) was observed in tea drinkers. CONCLUSIONS: Our data were suggestive of a reduced risk of BE and E with tea intake. An adverse effect of coffee was found among BE patients who had stopped drinking coffee. Coffee or tea intakes could be indicative of other lifestyle habits with protective or adverse impact on esophageal mucosa.

Hyperammonemic coma in a patient with late-onset OTC deficiency.

Urea Cycle Disorders ( UCD ) are among the most common genetic diseases of the metabolism and ornithine transcarbamylase deficiency (OTC), an X-linked defect is the most frequent among them. It is responsible for hyperammonemia that can lead to chronic neurological illness and potentially to death in case of delayed diagnosis and treatment. With regards to the OTC deficiency there is great clinical heterogeneity with early-onset phenotypes with mostly poor prognosis and late-onset phenotypes with a better one. In the article it is reported the case of a 8 years old patient with diagnosis of OTC deficit with late-onset phenotype. The kid was brought to our hospital because of continuous vomiting and gastro- intestinal disorders, associated with irritability and lethargy later resulted into coma. Measurement of plasma ammonia concentration, followed by measurement of plasma amino acid and urine orotic acid levels allowed to diagnose the OTC deficit, lately confirmed by molecular genetic studies. The patient has been promptly treated with Sodium Phenylbutyrate, Arginine and discontinuing the protein intake. Gradually the ammonemia value decreased, and general and neurological conditions improved with resolution of the coma. To conclude, for patients presenting unexplained neurological symptoms, confusion and decreased level of consciousness, up to coma, urea cycle disorders and in particularly OTC deficiency should be considered in the differential diagnosis and an urgent ammonia level determined. In case of hyperammonemia, the treatment should be started immediately , even without a precise ethiologic diagnosis.

The ProTect device in the treatment of severe fecal incontinence: preliminary results of a multicenter trial.

BACKGROUND: Patients suffering from severe fecal incontinence (FI) in whom surgical treatment has either failed or is inappropriate due to high operative risks and those who refuse to undergo surgery are condemned to living with their embarrassing symptoms, often responsible for progressive social isolation. ProTect is a new, relatively simple, medical device intended for selected patients suffering from severe FI. It consists of a pliable, silicone catheter with an inflatable balloon that seals the rectum at the anorectal junction, acting like an anal plug. The proximal part of the catheter incorporates two contacts that monitor the rectum for the presence of feces. The patient is alerted to an imminent bowel movement and, hence, a potential fecal accident, through a beeper. METHODS: A multicenter trial has been set up to assess the reliability of the device in preventing episodes of FI and to evaluate its impact on quality of life. Patients with significant FI (CCF>10) were prospectively entered into this 14-day study. Two quality of life questionnaires and a daily log of bowel activity and incontinent episodes were completed before and during the study. RESULTS: Currently, the study enrolled 17 patients and 11 patients (9 women, 2 men) with a mean age of 66 years (range, 46-85) completed the trial. In these 11 subjects, there was an overall significant improvement in the quality of life (p<0.05) and a significant reduction in incontinence scores (p<0.001) while using ProTect compared to baseline. CONCLUSIONS: The ProTect is a safe non-surgical device that is able to prevent episodes of FI. It is unique because it can be used according to a patient's needs without interfering with activities of daily living.

Treatment with botulinum toxin of octo-nonagerians with oesophageal achalasia: a two-year follow-up study.

BACKGROUND: Treatment of oesophageal achalasia with intrasphincteric injections of botulinum toxin has proved to be a successful alternative treatment modality. However, little is known about its long-term effects in very old patients. AIM: To evaluate the effects of such treatment in octo-nonagerians during a 2-year follow-up period. PATIENTS AND METHODS: Thirty-three patients with idiopathic oesophageal achalasia (range 81-94 years) entered the study. After basal evaluation and screening procedures, 100 U of botulinum toxin was injected at the lower oesophageal sphincter, and the procedure was repeated 1 month later. Data were collected at baseline and were compared after 1 and 2 years following the procedure. RESULTS: Seventy-eight per cent of patients were considered responders at 1 year and 54% were considered responders at 2 years. The weight gain at the end of the follow-up period was 2 (0-3) kg. No significant relationship was found between baseline lower oesophageal sphincter pressure and symptoms score after 1 and 2 years of follow-up; moreover, no major complications of botulinum toxin therapy were reported. CONCLUSION: Treatment of very old achalasic patients with botulinum toxin is safe, effective and yields good quality of life in a substantial proportion of these subjects.

Endoscopic treatment of gastroesophageal reflux disease.

Gastroesophageal reflux disease is a common chronic disorder which has a severe effect on the patient's quality of life. In view of the high cost of medical therapy and the limitations of surgery, a variety of endoscopic techniques have been developed for the treatment of this condition, and these have shown apparently encouraging results, at least in the short term. However, promising results have been obtained in only around two-thirds of patients over a short-term follow-up period of about 6 months. Moreover, several inconsistencies have emerged between the efficacy of this form of treatment in improving symptoms and quality of life and a lack of improvement of objective parameters, such as lower esophageal sphincter pressure and esophageal acid exposure. The authors strongly endorse the need for comprehensive evaluation of clinical evidence on this topic. After an extensive evaluation of existing literature, we suggest that controlled studies are urgently needed in order to clarify the potential of endoscopic therapy, either in terms of cost-effectiveness or in comparison with standard therapy. Meanwhile, with regard to current practice, the use of endoscopic treatment should be limited to clinical trials, which should incorporate the provision of comprehensive and unbiased information to study patients.

Segmental dilatation of the ileum presenting with acute intestinal bleeding.

The authors report a case of acute intestinal bleeding caused by ulcerated segmental ileal dilatation occurring in a 5-month-old infant. The profuse emission of dark red blood per rectum caused acute anemia (Hb 5.3 g/dL). Because of absence of any other sign and symptom and normal plain x-ray, a bleeding Meckel's diverticulum was suspected. Laparoscopy was performed showing the ileal dilatation, and through an enlarged port incision the bowel was exteriorized and resected. Histology results showed an ulcer caused by heterotopic gastric mucosa. The etiopathogenesis and clinical manifestations of segmental intestinal dilatation are discussed.

Long-term follow-up of achalasia patients treated with botulinum toxin.

AIMS: To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief MATERIALS AND METHODS: A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin. Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin. In the case of failure or relapse (symptom score >2), treatment was repeated. RESULTS: All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin. At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal). Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment. Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30). Up to day 31 (83.7%) patients were still in remission. We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053). Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5) CONCLUSIONS: Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief.

Antibody response to Helicobacter pylori CagA and heat-shock proteins in determining the risk of gastric cancer development.

OBJECTIVE: To investigate whether the systemic antibody response to Helicobacter pylori heat shock protein B can be considered, in addition to anti cytotoxin-associated protein [CagA) antibody determination, a further serological marker of increased risk of gastric cancer development. METHODS: A total of 98 Giemsa positive Helicobacter pylori patients (28 with gastric cancer, 30 with duodenal ulcer and 40 with nonulcer dyspepsia) were studied. Serum samples obtained from all patients were tested for IgG antibodies to CagA (116 kDa), VacA [89kDa) and heat skock protein B (54 kDa) antigens of Helicobacter pylori by the Western blot technique. RESULTS: 26/28 patients [(92.9% with gastric carcinoma, 29/30 patients [96.7%) with duodenal ulcer and 30/40 patients (75.0%) with non-ulcer dyspepsia were seropositive for CagA protein. The prevalence of serum IgG antibody to CagA in the cancer patients was not significantly higher than in duodenal ulcer and non-ulcer dyspepsia patients. The prevalence of antibodies to VacA was not significantly different between gastric carcinoma and non-ulcer dyspepsia patients. In contrast the prevalence of systemic antibodies to heat skock protein B was significantly higher in gastric cancer patients (78.6%) than in duodenal ulcer (36.7%, p=0.002) or nonulcer dyspepsia patients (52.5%, p=0.029). CONCLUSIONS: The detection of antibodies to heat shock protein B is proposed as an additional test which, in association with the determination of serum antibodies to CagA, could help in determining the risk of developing severe gastroduodenal disease, and gastric cancer, in particular.

A multicentre randomised study of intrasphincteric botulinum toxin in patients with oesophageal achalasia. GISMAD Achalasia Study Group.

BACKGROUND: Intrasphincteric injection of botulinum toxin (Botx) has been proposed as treatment for oesophageal achalasia. However, the predictors of response and optimal dose remain unclear. AIMS: To compare the effect of different doses of Botx and to identify predictors of response. PATIENTS/METHODS: A total of 118 achalasic patients were randomised to receive one of three doses of Botx in a single injection: 50 U (n=40), 100 U (n=38), and 200 U (n=40). Of those who received 100 U, responsive patients were reinjected with an identical dose after 30 days. Clinical and manometric assessments were performed at baseline, 30 days after the initial injection of botulinum toxin, and at the end of follow up (mean 12 months; range 7-24 months). RESULTS: Thirty days after the initial injection, 82% of patients were considered responders without a clear dose related effect. At the end of follow up however, relapse of symptoms was evident in 19% of patients who received two injections of 100 U compared with 47% and 43% in the 50 U and 200 U groups, respectively. Using Kaplan-Meier analysis, patients in the 100x2 U group were more likely to remain in remission at any time (p<0.04), with 68% (95% CI 59-83) still in remission at 24 months. In a multiple adjusted model, response to Botx was independently predicted by the occurrence of vigorous achalasia (odds ratio 3.3) and the 100x2 U regimen (odds ratio 3.2). CONCLUSIONS: Two injections of 100 U of Botx 30 days apart appeared to be the most effective therapeutic schedule. The presence of vigorous achalasia was the principal determinant of the response to Botx.

Long-term follow-up of achalasic patients treated with botulinum toxin.

Botulinum toxin A (BoTx), a potent inhibitor of acetylcholine release from nerve endings both within the myenteric plexus and at the nerve-muscle junction, has been shown to decrease the lower esophageal sphincter (LES) pressure in patients with achalasia. Because of this property, the esophageal injection of BoTx has been suggested as an alternative treatment in achalasia. The objective of this study was to determine the long-term efficacy and safety of intrasphincteric injection of BoTx in a group of achalasic patients. Nineteen patients (mean age 56.1 +/- 19.2 years) were enrolled in the study. All of them were injected endoscopically with 100 U of BoTx by sclerotherapy needle at different sites of the LES. Symptom score (dysphagia, regurgitation and chest pain, each on a 0-3 scale), esophageal manometer and esophageal radionuclide emptying were assessed before the treatment and at 4 weeks, 3 months and 1 year after BoTx injection. In case of failure or relapse (symptom score > 2), the treatment was repeated. All but five patients (74%) were in clinical remission at 1 month. Mean symptom score after 1 month of BoTx decreased from 7.1 +/- 0.9 to 2.2 +/- 2.5 (p < 0.05). LES pressure decreased from 38.4 +/- 13.7 to 27.4 +/- 13.5 mmHg (p < 0.05) and 10-min radionuclide retention decreased from 70.9 +/- 20.7% to 33.8 +/- 27.0% (p < 0.05). Side-effects (transient chest pain) were mild and infrequent. At 12 months, the clinical score was 0.9 +/- 0.5 (p < 0.05 vs. basal); mean LES pressure was 22.0 +/- 7.1 (p < 0.05 vs. basal) and 10-min radionuclide retention was 15.8 +/- 6.0% (p < 0.05 vs. basal). The efficacy of the first injection of BoTx lasted for a mean period of 9 months (range 2-14 months). At the time of writing (follow-up period mean 17.6 months, range 2-31), 14 patients (10 with one injection) were still in remission (74%). Our results showed that one or two intrasphincteric injections of BoTx resulted in clinical and objective improvement in about 74% of achalasic patients and are not associated with serious adverse effects; the efficacy of BoTx treatment was long lasting; this procedure could be considered an attractive treatment, especially in elderly patients who are poor candidates for more invasive procedures.

Comparison of two different formulations of botulinum toxin A for the treatment of oesophageal achalasia. The Gismad Achalasia Study Group.

BACKGROUND: Intrasphincteric injection of botulinum toxin has been reported as a safe and effective alternative treatment in oesophageal achalasia, especially in high-risk and elderly patients. AIM: : To compare two formulations of botulinum toxin in the management of achalasia. PATIENTS AND METHODS: We randomly compared the efficacy and safety of 100 U of Botox (Allergan, Irvine, USA) and 250 U of Dysport (Ipsen, Milan, Italy), injected through a sclerotherapy needle at the level of the lower oesophageal sphincter, in 78 consecutive patients with achalasia. Symptom score, oesophageal manometry and 24 h pH-metry were recorded (before and 1 month after therapy). Symptom score was also obtained 6 months after treatment. RESULTS: One month after treatment, the effects of the toxin on symptoms and oesophageal tests were similar for both formulations. Lower oesophageal sphincter pressure decreased from 31 +/- 12 to 18 +/- 5 mmHg after Botox, and from 35 +/- 9 to 18 +/- 10 after Dysport. At the end of the follow-up period (6 months), symptom score decreased from 5 +/- 1.2 to 1.2 +/- 0.8 after Botox and from 5.2 +/- 1.5 to 1.5 +/- 1 after Dysport. Moreover, the percentages of patients who failed to respond to treatment (10% and 17.5%) and who relapsed during follow-up (12% and 24%) did not differ significantly. No patient complained of reflux symptoms after treatment, although abnormal acid exposure was documented in two subjects. CONCLUSIONS: Both formulations of botulinum toxin have comparable efficacy in the treatment of oesophageal achalasia, for up to 6 months of follow-up.

Gastroprotection by 4-methylpyrazole against ethanol in humans.

4-Methylpyrazole (4-MP), a specific inhibitor of alcohol dehydrogenase, exerts gastroprotection of unusually long duration in rats. We tested the hypothesis that pretreatment with 4-MP might protect the human gastric mucosa against alcohol-induced acute injury. Fourteen healthy volunteers received pretreatment with either 4-MP, 15 mg/kg body weight dissolved in 50 ml of orange juice, or placebo and 2 hr later 100 ml of 40% ethanol. The endoscopic appearance of the gastric mucosa was evaluated and scored (scale 0-5) and mucosal biopsies were obtained just before pretreatment and 30 min after ethanol for histologic examination and prostaglandin E2 measurement. In the 4-MP group the mean endoscopic injury score was significantly lower than that in placebo group, in both the body and the antrum. Histologically, 4-MP significantly reduced disruption of surface epithelium and completely prevented the deep hemorrhagic mucosal lesions. In the 4-MP group no changes in gastric mucosal PGE2 levels were detected. In rats, 4-MP did not inhibit gastric acid output, whereas it markedly increased the adherent gastric mucus evaluated by the alcian blue recovery method. When lipid peroxidation was induced by carbon tetrachloride in hepatic microsomes, 4-MP caused significant inhibition of malondialdehyde generation. We conclude that 4-MP provides significant protection of the human stomach against alcohol-induced acute mucosal injury. 4-MP, besides inhibiting the conversion of alcohol to acetaldehyde, might protect the gastric mucosa by increasing adherent gastric mucus and by scavenging free radicals.

Characterization of acid and alkaline reflux in patients with Barrett's esophagus. G.O.S.P.E. Operative Group for the study of Esophageal Precancer.

Although the pathogenic role of gastroesophageal reflux in Barrett's esophagus is widely accepted, the pattern of gastric and esophageal pH profile of patients with Barrett's esophagus is not well documented. Moreover, the observation that a columnar-lined esophagus can also develop after gastrectomy implies that chronic irritation of the lower esophagus by duodenal juice can be as harmful as acid reflux. To test this hypothesis, we simultaneously monitored gastric and esophageal pH in 19 patients with endoscopically and histologically proven Barrett's esophagus, in 35 with slight-to-moderate esophagitis and in 10 healthy subjects. The gastroesophageal reflux pattern in both Barrett's esophagus and esophagitis was characterized by mainly acid refluxes. Esophageal acid exposure (% time pH < 4) was 39.4 in patients with Barrett's esophagus, 14.6 in patients with esophagitis (P < 0.05), and 3.1 in healthy subjects (P < 0.05). Seven of 19 patients with Barrett's esophagus and 7 of 35 with esophagitis had evidence of alkaline reflux too; but pure alkaline refluxes accounted for only 1.9% of total time in Barrett's esophagus and 0.3% in esophagitis patients. In conclusion, these results confirm the high prevalence and severity of acid reflux in patients with Barrett's esophagus and show that the reflux of pure alkaline material into the esophagus is a rare event in both Barrett's esophagus and esophagitis patients.

Primary mucinous carcinoma of the skin. Report of case.

The authors report a case of a primary mucinous carcinoma of the skin. This is a rare adnexial tumor arising from the eccrine secretory coils. The histologic characteristic finding of this lesion is the heap of abundant mucinous material (sialomucin) in the dermis in which rare epithelial islands are free-floating. In this study we also value the importance of a correct diagnosis for an appropriate therapy.

Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR.

Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose).

An ultrasonographic method to measure the sensitivity of the baroreflex in clinical practice: application to pharmacological studies.

To determine whether it is possible to assess baroreceptor sensitivity by measuring changes in blood velocity in the carotid artery and changes in the heart rate, we performed a series of 108 experiments in 19 hypertensives aged 20-57 years (mean 46.6 +/- 8.6). In each experiment, we took simultaneous measurements of carotid artery blood flow velocity (Doppler technique), the brachial intra-arterial blood pressure and the heart rate, during a rapid and transient increase in blood pressure induced by injections of phenylephrine. We then calculated the maximum slope of the regression lines correlating blood velocity with the heart period (Trieste method) and blood pressure with the heart period (Oxford method). We obtained good accuracy from the Trieste method compared with the Oxford method, as assessed by the mean of the sum of the squares (difference + 5%, NS). After the administration of 4 mg oral lacidipine to 13 essential hypertensives, aged 37-54 years (47.6 +/- 5.3), baroreflex sensitivity was not changed, as assessed by either method (Oxford method 10.1 +/- 5.5 versus 9.8 +/- 6.2 ms/mmHg; Trieste method - 0.57 +/- 0.32 versus - 0.49 +/- 0.31 ms/Hz). The coefficients of variation for the two methods, calculated for the measurements taken before and after the administration of lacidipine, were not statistically different (Oxford method 25.0 +/- 18.4 versus 36.2 +/- 16.0; Trieste method 36.7 +/- 19.2 versus 39.7 +/- 19.2). The new non-invasive Trieste method thus showed the same accuracy and precision as the invasive Oxford method in measuring baroreflex sensitivity and can be used in pharmacological studies.