Comparative effects of three cytokine regimens after high-dose cyclophosphamide: granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and sequential interleukin-3 and GM-CSF.

PURPOSE: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m(2)), given as the first step of a high-dose sequential chemotherapy. PATIENTS AND METHODS: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 microg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34(+) cells and granulocyte-macrophage colony-forming units (CFU-GM). RESULTS: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P <.0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P =.028). The peak of CD34(+) cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P =.0002), whereas the median peak value of CD34(+) cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. CONCLUSION: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF-treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.

[Comorbidities in rheumatoid arthritis: analysis of hospital discharge records]. / Comorbidità nell'artrite reumatoide: un'analisi delle schede di immissione ospedaliera.

OBJECTIVE: Arthritis is often associated with comorbidities. For many of them, such as hypertension, cardiovascular disease, chronic pulmonary disease, and upper gastrointestinal disease, arthritis and its treatment may also represent a risk factor. This study is concerned with an evaluation of the frequency of comorbidities in a cohort of patients with rheumatoid arthritis (RA). METHODS: The discharge diagnoses of patients with RA during the period 1 January 1997 to 31 December 2000 were retrieved from the database of the Department of Internal Medicine of the University of Genova, Italy. The diagnosis of RA was made if the patient's discharge record contained the code 714 of the International Classification of Diseases, IX revision, as first 3 numbers. The other diagnoses were also recorded along with demographic data, type and duration of hospital stay, and performed procedures. RESULTS: During the study period, 427 patients with RA were admitted to the hospital for a total number of 761 admissions, which represented 2.2% of total admissions. Ninety-one (21.3%) patients did not have comorbidities, whereas 336 (78.6%) had one or more comorbidities. The most frequently observed comorbidities were cardiovascular diseases (34.6%), including hypertension (14.5%) and angina (3.5%), followed by gastrointestinal (24.5%), genito-urinary (18.7%) and respiratory (17%) diseases. There was a male predominance (p=0.004) within patients with comorbidities, who were significantly older (64.2+/-3.2 years vs. 57.2+/-4.2 years; p<0.001) and required longer periods of hospital stay (22.7 days vs. 12.5 days; p<0.001). CONCLUSIONS: Comorbidities are present in nearly 80% of RA inpatients. Comorbidity is a good predictor of health outcome, health services utilization, and medical costs. Because RA comorbidity can act as confounder, it should be considered in epidemiologic studies and clinical trials.

In vitro synergistic inhibition of human bone marrow hemopoietic progenitor growth by a 3'-azido-3'-deoxy-thymidine, 2',3'-dideoxycytidine combination.

In vitro growth of human normal bone marrow granulocyte-macrophage colony forming units (CFU-GMs) and erythroid burst forming units (BFU-Es) was dose-dependently inhibited by 3'-azido-3'deoxythymidine (AZT) (from 0.1 microM to 4 microM) and 2',3'-dideoxycytidine (ddC) (from 0.01 microM to 1.0 microM). These ranges included minimum in vitro inhibitory concentrations to HIV-1 and concentrations corresponding to plasma level achievable in vivo. A synergistic inhibitory effect, statistically highly significant, was observed when combinations of the two drugs were added to cultures. This severe in vitro toxicity of ddC and the synergistic toxicity of AZT-ddC combinations on hemopoietic progenitor cells should be considered when the two drugs are administered in concurrent or alternating regimens.

Oncological research overview in the European Union. A 5-year survey.

This study evaluates the distribution of papers published by European Union (EU) authors in oncological journals from 1996 to 2000, and compares the results with those of a previous study carried out in 1995. The impact of oncological research in the EU is compared with that of the United States (US) and the world, and research trends are highlighted through an analysis of keywords. Data on articles published in oncological journals (ISI Subject Category=ONCOLOGY) selected from Current Contents/Life Science and Current Contents/Clinical Medicine (1996-2000) on the weekly diskette version were downloaded. Mean Impact Factor (IF), source country population and gross domestic product (GDP) were analysed. A special-purpose software to determine the most commonly used keywords was utilised. From 1996 to 2000, 66021 papers were published in the world in oncological journals: 35.5% came from the EU (UK, Italy, Germany, France and The Netherlands ranking the highest) and 38.8% from the US. The total number of EU papers increased from 4063 in 1995 to 4843 in 2000. Compared with the previous study, no important changes were seen, with the top five countries in 1995 maintaining their ranking in 2000. However, some small countries (Denmark, Norway and Ireland) fared worse in 2000, while others (France, Germany and Greece) improved their position. The mean IF for the EU papers was 2.9 compared with 4.0 in the US. The mean IF increased for all of the nations. In particular, while France and Germany showed a very positive performance trend in their respective IFs, countries such as Norway, Denmark and Italy showed less improvement. The analysis of keywords appearing in articles written in 2000 showed that the leading fields of research were breast cancer in the diseases category of keywords, cisplatin and platinum compounds in the drugs category, radiotherapy in the treatment category and apoptosis in the experimental studies category. Variety in the use of keywords should be avoided, and journal editors should encourage their standardisation.

Assessing oncological productivity. is one method sufficient?

This work analyses the distribution of oncological papers published in 1995 by authors from the European Union (EU) in any journal of all the Subject Categories of the Science Citation Index compiled by ISI (Institute for Scientific Information, Philadelphia, USA) and is based on the country of origin of all of the contributors. The study compares the results with those of a previous study dealing with publications in journals of the ISI Oncology Category based on the country of origin of the corresponding author. The aim of the study was to compare two different methods used to evaluate research productivity in order to understand the extent to which the results are influenced by the methodology adopted. Data on the number of published papers for each country, ratio between the number of occurrences of papers and country population and gross domestic product (GDP), and mean Impact Factors (IF ) were compared. While findings on the number of published papers (United Kingdom (UK), Germany and France ranking best), source country population (Sweden, Denmark and the Netherlands ranking best) and gross domestic product (Sweden, Finland and the Netherlands ranking best) showed no important changes, the mean IF value result was, for some countries, very different from the previous study. In particular, while Germany, Belgium, Portugal and France fared well, Norway, Sweden, Austria and Spain showed poorer results. Some hypotheses are advanced, and care in the scientometric interpretation of data is urged. An analysis of the journals in which EU authors published their articles was also carried out and the main SCI categories to which the journals belong are reported. As was expected, many categories other than oncology were represented (biochemistry, haematology, pathology, etc.).

Impact assessment of oncology research in the European Union.

In this study the distribution of papers published by authors from the European Union (EU) in oncological journals was analysed, as was the impact of oncological research in the EU compared with that produced in other countries. Papers published during 1995 in the oncological journals listed by ISI (Institute for Scientific Information, Philadelphia, U.S.A.) were downloaded. The parameters of impact factor (IF), source country population and gross domestic product (GDP) were considered. An analysis of the key words, both those reported by the authors and those attributed by ISI, was carried out using a special purpose program. 36.5% of papers published in oncological journals come from the EU (the U.K., Italy, Germany and France ranking at the top) and 40.7% from the U.S.A. The mean IF was 2.4 for EU papers, 3.3 for the US and 2.4 for other countries. Our data confirm that smaller countries performed better than larger ones. The key words analysis shows that the leading fields of research were breast cancer for diseases, cisplatin for drugs and p53 for experimental studies. A standardisation of key words on behalf of journal editors is proposed.

Value of programmed ventricular stimulation in predicting sudden death and sustained ventricular tachycardia in survivors of acute myocardial infarction.

To assess the prognostic value of the response to programmed ventricular stimulation in selected post-acute myocardial infarction (AMI) patients identified at risk of sudden death and spontaneous sustained ventricular tachycardia (VT) (arrhythmic events) by noninvasive, highly sensitive testing, 286 consecutive patients were evaluated prospectively and followed for 12 months. One hundred three patients (group 1) with either left ventricular ejection fraction < or = 40% or ventricular late potentials or spontaneous complex ventricular arrhythmias were considered at risk of late arrhythmic events and eligible for programmed ventricular stimulation; the remaining 183 patients (group 2) were discharged without any further evaluation. Electrophysiologic study was performed 11 to 20 days after AMI utilizing up to 2 extrastimuli and rapid ventricular burst pacing. At the end of the follow-up period, 10 patients in group 1 and 2 in group 2 died of cardiac causes; in addition, 10 patients in group 1 and 1 in group 2 had arrhythmic events. Sustained monomorphic VT was the only inducible arrhythmia related either to cardiac death (p <0.0005) or to arrhythmic events (p <0.0001). It was induced in 11 patients (3 died suddenly, and 3 had spontaneous VT). Multivariate analysis showed that such arrhythmia was the strongest independent predictor of arrhythmic events (F = 9.76; p <0.0001). In the entire study population, it allowed identification of patients at risk, with a sensitivity, specificity, and positive predictive value of 55%, 99%, and 67%, respectively. We conclude that programmed ventricular stimulation performed in selected post-AMI patients, utilizing a moderately aggressive stimulation protocol, is a specific but less sensitive procedure for predicting arrhythmic events; the induction of sustained monomorphic VT allows the accurate identification of patients who may profit by prophylactic antiarrhythmic therapy.

Frequency, characteristics and significance of supraventricular tachyarrhythmias detected by 24-hour electrocardiographic recording in the late hospital phase of acute myocardial infarction.

The incidence, characteristics and clinical significance of supraventricular tachyarrhythmias occurring in the late hospital phase of acute myocardial infarction (AMI) were assessed in 209 consecutive patients. Arrhythmias were quantified by 24-hour electrocardiographic recording 16 +/- 3 days after AMI, and were classified according to the degree of complexity in 5 classes. Class 0 = less than 5 premature beats/hr; class 1 = between 5 and 100/hr; class 2 = greater than 100/hr or repetitive premature beats; class 3 = atrial-junctional tachycardia; class 4 = atrial flutter-fibrillation. Supraventricular tachyarrhythmias classes 1 to 2 always occurred in the absence of symptoms in 86 patients (41%); supraventricular tachyarrhythmias classes 3 to 4 (paroxysmal, self-limiting, brief) occurred in 27 patients (13%), symptomatically in 6. The presence of supraventricular tachyarrhythmias classes 2 to 3 was related to age over 55 years and complex ventricular tachyarrhythmias (greater than 20 premature beats/hr, ventricular tachycardia) (both p less than 0.05). Increasing complexity of supraventricular tachyarrhythmias was significantly associated with presence and entity of cardiac enlargement and left ventricular dysfunction (both p less than 0.01). Patients with class 4 showed the most severe cardiac deterioration. During the 2 years after AMI, patients with classes 2, 3 and 4 had a higher incidence of acute pulmonary edema, New York Heart Association functional classes III to IV for congestive heart failure (both p less than 0.005) and a greater need of digitalis and diuretics (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of omeprazole 20 and 40 mg twice daily on intragastric acidity in duodenal ulcer patients.

BACKGROUND: The combination of omeprazole with amoxycillin or clarithromycin is used as treatment against Helicobacter pylori. It seems likely that the antibacterial activity of the antibiotic may be improved by increasing gastric pH towards neutrality, and a twice daily regimen of omeprazole is probably needed. AIM: To assess the effects of twice daily administration of omeprazole 20 and 40 mg. METHODS: Twelve duodenal ulcer patients in remission were randomized to receive in single-blind fashion either placebo, omeprazole 20 mg or omeprazole 40 mg twice daily (08.00 and 20.00 h). On the sixth day of dosing they underwent 24-h gastric pH-metry. RESULTS: Omeprazole 20 and 40 mg b.d. produced marked decreases (P < 0.001) of 24-h gastric acidity (pH 5.4 +/- 0.9 and pH 5.7 +/- 0.6, respectively, vs. a basal pH of 1.4 +/- 0.2) and kept gastric pH at levels higher than 3.0 for almost 24 h. Gastric pH was kept above 5.0 for about 18 h and above 6.0 for about 10 h, while the time spent above 7.0 did not exceed 3 h. There were no significant differences between the two omeprazole dosages at any pH threshold. CONCLUSION: Omeprazole 20 mg b.d. is sufficient to render the gastric milieu as anacidic as possible in duodenal patients.

Comparison of 24-h control of gastric acidity by three different dosages of pantoprazole in patients with duodenal ulcer.

BACKGROUND: It is now clear that the extent to which gastric acid secretion must be suppressed varies with the clinical condition being treated. AIM: To assess the 24-h control of gastric acidity and the individual response variability of three different doses of pantoprazole. METHODS: Sixty-four duodenal ulcer patients were recruited for this prospective, randomized, multicentre, double-blind, parallel-group study. They were subdivided into three well-matched groups treated with 20 mg o.m., 40 mg o.m. and 40 mg b.d. of pantoprazole, respectively. Endoscopy and intragastric pH monitoring were performed in each patient before and after 14 days of treatment. RESULTS: Fifty-five patients were eligible for final analysis (17 treated with 20 mg o.m., 18 with 40 mg o.m. and 20 with 40 mg b.d. pantoprazole). The ulcer crater healed in 94, 88 and 95% of cases, respectively. The three dosages of pantoprazole produced significant increases in gastric pH compared to basal levels (P < 0.0001). There was also a clear dose-dependent pharmacodynamic effect, which augmented on moving from the lowest dosage of 20 mg o.m. pantoprazole to the highest dosage of 40 mg b.d. (P < 0.01-0.001). The inter-individual response variability within the three treatment groups was more marked with the dose of 20 mg than with the two higher doses of pantoprazole. CONCLUSIONS: All three doses of pantoprazole we tested are highly effective in decreasing gastric acidity and there is a clear dose-dependent pharmacodynamic effect on moving from the lowest to the highest dosage. The greatest inter individual variation in the degree of acid inhibition was seen with pantoprazole 20 mg o.m., while the majority of patients responded adequately to the two higher doses of the drug.

Head-to-head comparison of 1-week triple regimens combining ranitidine or omeprazole with two antibiotics to eradicate Helicobacter pylori.

BACKGROUND: Triple therapies containing omeprazole and ranitidine have been shown to be equivalent in eradicating H. pylori infection, but have been assessed either separately or head-to-head, only in small trials. AIM: To carry out a large randomized controlled study comparing omeprazole and ranitidine combined with two antibiotic combinations for 1 week. METHODS: Three hundred and twenty H. pylori-positive patients were randomly subdivided into four equal-sized groups and received one of the following treatments: OAM = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; RAM = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; OAC = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s.; RAC = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s. The assessment of H. pylori status was performed before and 4 weeks after the end of therapy by means of CLO-test and histology. H. pylori infection was considered to be eradicated when both tests were negative. RESULTS: OAM and RAM eradicated H. pylori in 89% and 85% of cases on per protocol (P = 0.48) and in 77% and 75% of cases on intention-to-treat analyses (P = 0.71). OAC and RAC eradicated H. pylori in 67% and 70% of cases on per protocol (P = 0.68) and in 57% and 64% of cases on intention-to-treat analyses (P = 0.41). In contrast, there was significant difference between OAM and OAC (P<0.01) and between RAM and RAC (P<0.05). Side-effects occurred in 15%, 10%, 17% and 16% of patients with respect to the above four subgroups. CONCLUSIONS: Omeprazole and ranitidine combined with two antibiotics for 1 week are equally effective in the eradication of H. pylori infection, and these results question the role of profound acid suppression in the eradication of the bacterium.

Circadian pattern of intragastric acidity in patients with non-erosive reflux disease (NERD).

BACKGROUND: Most patients with gastro-oesophageal reflux disease have non-erosive reflux disease. Proton pump inhibitors are less effective than expected in these patients, but no previous study has measured their 24-h gastric pH values. AIMS: To evaluate whether there are differences in 24-h intragastric acidity between reflux patients with and without oesophagitis and controls. The influence of Helicobacter pylori on the gastric pH of reflux patients was also assessed. METHODS: Sixty-three consecutive patients with gastro-oesophageal reflux disease symptoms who agreed to undergo endoscopy and 24-h pH-metry were recruited. Twenty-five (39%) had erosive oesophagitis and 38 (61%) did not. H. pylori was diagnosed by CLO test, histology and 13C-urea breath test. Gastric pH was also measured in 30 controls without digestive symptoms. RESULTS: H. pylori was found in seven of the 25 (28%) patients with oesophagitis and 14 of the 38 (37%) patients with non-erosive reflux disease. Oesophageal pH-metry was abnormal in 21 of the 25 (84%) patients with oesophagitis and in 32 of the 38 (84%) patients with non-erosive reflux disease. The median gastric pH did not differ between patients with and without oesophagitis or between them and controls during the 24 h (P = 0.8) and other time intervals (P = 0.2-0.4). The gastric pH did not differ between infected and non-infected patients with oesophagitis (P = 0.2-0.4) or non-erosive reflux disease (P = 0.3-0.8). CONCLUSIONS: The circadian pattern of intragastric acidity does not differ between patients with non-erosive reflux disease and oesophagitis. Moreover, the study confirms that H. pylori infection does not affect the gastric pH in either group of reflux patients.

A new 1-week therapy for Helicobacter pylori eradication: ranitidine bismuth citrate plus two antibiotics.

BACKGROUND: One-week triple regimens are currently the most recommended therapy for the eradication of Helicobacter pylori. No previous study has evaluated the efficacy of a short-term regimen combining ranitidine bismuth citrate with two antibiotics. METHODS: Seventy-two consecutive H. pylori-positive dyspeptic patients were recruited for this randomized, three-centre, open, parallel-group study. They were subdivided into two groups receiving either ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (group A) or ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s (group B) for 1 week. H. pylori infection was assessed by CLO-test and histology on both antral and corpus biopsies before and at least 4 weeks after the end of therapy. The bacterium was considered eradicated when both tests were negative. Eradication rates and the number of side-effects were evaluated in each group. The Chi-squared test was used for statistical analysis. RESULTS: One patient with only CLO-test positivity was erroneously randomized to group B and four patients dropped out of the study (two in group A and two in group B), mainly because they refused the second endoscopy. In group A, H. pylori was eradicated in 31 of 36 patients (intention-to-treat = 86%; 95% CI = 71-95% and per protocol 31/34 = 91%; 95% CI = 76-98%). Side-effects occurred in 10 patients (27%) and they were generally mild. In group B, H. pylori was eradicated in 29 of 35 patients (intention-to-treat = 83%; 95% CI = 66-93%; and per protocol 29/33 = 88%; 95% CI = 72-97%). Seven patients (20%) complained of modest side-effects. There was no significant difference between the two treatment arms (P = N.S.): no severe adverse events occurred and none of the patients was withdrawn from the study because of them. CONCLUSIONS: The co-administration of ranitidine bismuth citrate plus clarithromycin at low dosage and metronidazole in twice daily doses for 1 week is a short, effective and well-tolerated regimen for the eradication of H. pylori. These findings should provide the impetus for large-scale investigations.

Inaccuracy of hourly sampled pH measurements in describing the effect of antisecretory drugs on circadian gastric acidity.

This study was carried out in order to verify whether gastric pH measurements obtained with continuous monitoring are more accurate in assessing the pharmacodynamic properties of antisecretory drugs than those obtained with the traditional hourly nasogastric aspiration method. Accordingly, we compared the most commonly used acidity indexes (median of pHs and mean of [H+]s) and the total circadian time spent above 4.0 pH units, all of which were calculated from both raw data sampled at rates of a few seconds with modern apparatus and data obtained from the same profiles scanned punctually at a 60 minute rate. The analysis referred to 231 continuous gastric pH-metries which were performed over the circadian period to evaluate the acid inhibitory effects of different doses and dosage regimens of various H2-antagonists. In the population as a whole, the numbers and percentages of subjects, whose 60-minute sampled medians of pHs and means of [H+]s differed by less than +/- 10% from those obtained from raw fast-acquired data, were 107 (46%) and 34 (15%), respectively. There was even less agreement in the case of the circadian time above 4.0 pH units (26 cases = 11%). No statistical difference (P = .7) between the concordance rates of each variable in the three groups was observed. Considered simultaneously, there was concordance of the above three indexes in only seven out of the 231 cases. These results show that the hourly sampling rate fails to represent adequately gastric acidity changes induced by antisecretory drugs, due to the scarcity of experimental points. The acidity indexes calculated from these slowly sampled data are inaccurate, especially when the means of [H+]s are considered, and the duration of action of the drug often is defined randomly.

Twenty-four-hour control of gastric acidity by twice-daily doses of placebo, nizatidine 150 mg, nizatidine 300 mg, and ranitidine 300 mg.

This study was carried out to assess the effects on gastric acidity of placebo twice daily (bid), nizatidine 150 mg bid, nizatidine 300 mg bid, and ranitidine 300 mg bid by means of continuous 24-hour intragastric pH monitoring. Twelve patients with duodenal ulcer in remission were randomized to receive in single-blind fashion the above medications on four separate occasions, at least 1 week apart. The three active regimens produced higher pH values (P < .001) and maintained gastric pH above 3.0 units for a longer period (P < .001) than placebo in all time intervals but evening. Nizatidine 150 mg bid caused a lower rise in pH than nizatidine 300 mg bid (P < .01) and ranitidine 300 mg bid (P < .05) during both the daytime and the whole 24 hours. In these time windows also the time spent above 3.0 pH units was significantly shorter for the former regimen than for 300 mg bid of both nizatidine (P < .01) and ranitidine (P < .05). There was no difference between the latter two dosing schedules in terms of both potency and duration of action in all the time intervals considered. It is concluded that twice daily doses of H2 blockers are more effective than placebo in reducing gastric acidity. Three hundred milligrams twice daily of both nizatidine and ranitidine produce a significantly greater and longer-lasting acid suppression than 150 mg bid of nizatidine. Our study also confirms the greater effectiveness of H2 antagonists during nighttime than during day-time.

Single bedtime dose of famotidine: assessment of its antisecretory action by 24-hour intragastric pH monitoring.

The antisecretory efficacy of a single bedtime dose of famotidine, a new potent H2-receptor antagonist, was evaluated by means of continuous 24-hour intragastric pH monitoring. Of 20 patients with duodenal ulcers, ten randomly received famotidine 40 mg at 10 PM and ten were monitored without medication for control. Famotidine regimen led to a remarkable reduction of gastric acidity in patients who were treated for duodenal ulcer and the drug-induced pH levels were significantly different (P less than .0001) from those of untreated controls. The antisecretory action lasted for 12 hours, which comprised the nocturnal period, whereas no important difference was found between the two groups for the most part of the daytime. The drug was able to keep intragastric pH above 4 units during almost 50% of the whole 24-hour period. These results confirm that famotidine is a powerful and long-acting H2 blocker that relieves gastric acidity during the night and morning hours when administered as a single bedtime dose of 40 mg.

Bolus infusion of famotidine: effects on gastric pH by repeated 12-hour doses of 20 mg in postoperative patients.

This study was carried out to assess the efficacy of intravenous (IV) famotidine in suppressing gastric secretion over a 48-hour period. Twenty postoperative patients requiring a nasogastric tube received famotidine 20 mg IV every 12 hours and gastric pH was measured continuously by means of an indwelling probe. A baseline recording was performed over the first 4 hours and then the drug was infused every 12 hours (q12h) over a 15-minute period for the subsequent 48 hours. The mean pH value achieved during each time segment under active treatment was significantly higher (P < .001) than the mean basal value. Also the density distributions of minutes spent at the various pH units confirm that famotidine is highly effective (P < .001) in raising and maintaining gastric pH above 4.0 units during most of the drug-related period (44 hours). It can be concluded that repeated intravenous boli of famotidine 20 mg every 12 hours allow us to obtain an effective control of intragastric acidity. The antisecretory action is consistent over the total 48-hour period examined and therefore the use of intermittent infusion of famotidine seems to be advisable, as opposed to the recommended continuous IV administration of cimetidine and ranitidine. There is, however, a considerable intersubject variability in the antisecretory response to the drug.

Intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) co-expression in cutaneous malignant melanoma lesions.

The expression of intercellular adhesion molecule-1 (ICAM-1) and granulocyte-macrophage colony stimulating factor (GM-CSF) was investigated in 25 melanoma patients by evaluating 34 fresh biopsy specimens. ICAM-1 in situ hybridization and immunochemistry for ICAM-1 and GM-CSF were performed. Most of the metastatic melanoma samples (12 out of 18) and a few of the primary melanoma lesions (three out of 16) showed ICAM-1 expression. The expression of ICAM-1 was significantly (P < 0.01) higher in metastatic lesions than in primary tumours. GM-CSF mRNA and protein were detected in 10 of the 18 metastatic samples and in two of the 15 primary lesions. A significantly high degree (P < 0.0002) of concordance between ICAM-1 and GM-CSF expression was observed: the samples that were negative or positive for ICAM-1 expression were correspondingly negative or positive for GM-CSF. Correlation with clinical and histological parameters was examined. The expression of both molecules in metastatic samples was found to be significantly (P < 0.001) associated with a shorter recurrence-free period. These findings, if confirmed by a wider number of patients, could suggest the prognostic value of the simultaneous, and probably co-ordinated, expression of ICAM-1 and GM-CSF. They also highlight the importance of preventive molecular and biochemical characterization of neoplastic cell cytokine receptors, specifically focusing on the particular cytokine to be used as anticancer therapy and/or as adjunct to chemotherapy.

Prevalence of self-reported peripheral joint pain and swelling in an Italian population: the Chiavari study.

OBJECTIVE: To evaluate the prevalence of self-reported joint pain and swelling in the peripheral joints of subjects from an Italian general population. To correlate the result with demographic data and physical activity. METHODS: A total of 4,456 subjects aged 16 years or more listed in four general practices were invited to participate in the study and to fill out the ARC questionnaire. The 3,294 responders were asked to report: (a) any past occurrence of joint swelling lasting more than 4 weeks and the distribution of the swollen joints on a mannequin; (b) any joint pain lasting more than 4 weeks; (c) current joint pain or swelling; (d) morning stiffness; (e) whether they had been previously told by a doctor they had arthritis; and (f) their physical activity according to a three-class scale. RESULTS: Joint pain was reported by 889 (27%) subjects and joint swelling was reported by 463 (14%) subjects. Women reported joint pain and swelling more frequently than men, except for the younger age classes. The prevalence of joint pain and swelling increased with age in both sexes until age 55-64, when a plateau was observed. Age was involved in the determination of joint pain and swelling. Physical activity was involved only marginally. CONCLUSIONS: We found high levels of prevalence of pain and swelling in the peripheral joints in a general Italian population. Prevalence was higher in Italian subjects than in subjects from China and Pakistan studied using the same questionnaire. These differences may reflect cultural and social diversity in the perception of disease, as well as true differences in the prevalence of rheumatic symptoms across the world.

Absence of tolerance in duodenal ulcer patients treated for 28 days with a bedtime dose of roxatidine or ranitidine.

There is much experimental work on the occurrence of tolerance to the antisecretory effect of H2-receptor antagonists in healthy subjects, while data on its development in patients with duodenal ulcer are poor and conflicting. Moreover, this phenomenon has not been studied previously with 24 h gastric pH-metry in patients with active duodenal ulcer. For these reasons, we carried out a prospective pharmacodynamic investigation in 48 patients with endoscopically proven duodenal ulcer using the well-established once daily dosing schedule of H2 blockers. They were studied by means of 24 h continuous endoluminal pH-metry which was performed before, on d1 and d28 after receiving an oral bedtime dose (2200 hours) of either roxatidine 150 mg or ranitidine 300 mg, given in randomized and single-blind fashion. Eight patients did not complete the study for various reasons and 82% of ulcers healed after 4 weeks of therapy. Gastric pH was higher (P < 0.001) on d1 and d28 than basal values during all time periods, but the evening, with both H2 blockers. There was no significant difference between pH values of d1 and d28 in any time interval with both roxatidine and ranitidine. There was also no difference in pharmacodynamic data between the two active treatments. We conclude that tolerance does not develop after 1 month's treatment with a bedtime dose of H2 antagonist in patients with active duodenal ulcer and therefore data gathered on this phenomenon in healthy subjects are not applicable to ulcer patients.