Tyrphostins: tyrosine kinase blockers as novel antiproliferative agents and dissectors of signal transduction.

Protein tyrosine kinases (PTKs) are members of a growing family of oncoproteins and protooncoproteins that play a pivotal role in normal and abnormal proliferative processes. This hallmark identifies these unique proteins as potential targets for antiproliferative therapy. This review discusses the current status of PTK inhibitors, with special emphasis on tyrphostins as antiproliferative agents and as potential drugs for cancers, leukemias, psoriasis, and restenosis as well as other proliferative conditions. The development of tyrphostins as selective signal blockers can be viewed as a first step toward the development of "smart" cocktails as antiproliferative agents. Each of these custom-made cocktails will be aimed at proliferative conditions whose transduction pathways can be characterized by molecular tools. The review also discusses the use of PTK blockers as tools to study signal transduction processes in which protein tyrosine kinases are implicated.


Thrombospondins: structure and regulation of expression.

Thrombospondin (TSP) is a large, trimeric, modular glycoprotein that is a major constituent of platelet alpha granules. TSP is also secreted by a wide variety of epithelial and mesenchymal cells in patterns that reflect developmental changes in the embryo and response to injury in the adult. In addition to its role in blood coagulation, TSP has been reported to serve both adhesive and anti-adhesive functions, to foster neurite outgrowth, stimulate and inhibit cell growth and migration, and inhibit angiogenesis. Although this diversity in apparent function can be attributed, in part, to the ability of a single TSP to interact with several different cell-surface receptors, it is now known that the TSPs are encoded by at least three homologous genes in both human and mouse. TSP1, the commonly recognized protein isolated from platelets, is similar to TSP2 in structure. Both proteins contain NH2-terminal, COOH-terminal, and procollagen homology domains, and type I (TSP or properdin), type II (EGF-like), and type III (Ca(2+)-binding) repeats. However, the two TSPs differ in amino acid sequence and in the regulation of their expression. TSP1 is rapidly induced by serum and growth factors. An SRE and a binding site for NF-Y have been shown to mediate the serum response of the human TSP1 gene. On the other hand, TSP2 is far less responsive to serum than TSP1 and lacks the promoter elements that mediate the serum responsiveness of TSP1. TSP3 resembles TSP1 and TSP2 in its COOH-terminal domain and type III repeats, but contains four rather than three type II repeats and lacks type I repeats and a procollagen homology. The NH2-terminal domain of TSP3 also differs from that of either TSP1 or TSP2. All three TSPs demonstrate characteristic patterns of expression in the developing and adult mouse. It is therefore likely that each protein subserves a discrete function. In the future it will be necessary to distinguish among the three TSPs in addressing the function of these proteins.


Transcription by RNA polymerase II: initiator-directed formation of transcription-competent complexes.

Studies of transcription by RNA polymerase II have revealed two promoter elements, the TATA motif and the initiator (Inr), capable of directing specific transcription initiation. Although binding to the TATA motif by one of the components of the transcription machinery has been shown to be the initial recognition step in transcription complex formation, many promoters that lack a traditional TATA motif have recently been described. In such TATA-less promoters, the Inr element is critical in positioning RNA polymerase II. Various Inr elements have been described and classified according to sequence homology. These Inr elements are recognized specifically by Inr-binding proteins. Interaction between these Inr-binding proteins and components of the basal transcription machinery provides a means through which a transcription competent complex can be formed.


Glucocorticoid regulation of phenylethanolamine N-methyltransferase in vivo.

In vivo, supraphysiological doses of glucocorticoids are required to restore adrenal medullary phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28) activity after hypophysectomy. However, in vitro, phenylethanolamine N-methyltransferase gene expression appears normally glucocorticoid-responsive. To explore this paradox, rats were given dexamethasone or the type II-specific glucocorticoid RU28362 (1-1000 micrograms/day), and adrenal phenylethanolamine N-methyltransferase activity and mRNA levels were determined. At low doses (1-30 micrograms/day), neither steroid altered mRNA whereas at higher doses (100-1000 micrograms/day), mRNA rose 10- to 20-fold, with dexamethasone approximately 3 times as potent as RU28362. In contrast, enzyme activity fell with low doses of either steroid, consistent with suppression of ACTH and endogenous steroidogenesis. At higher doses of RU28362, enzyme activity remained low and unchanged despite increased mRNA expression, whereas higher doses of dexamethasone progressively restored the enzyme to normal. These findings suggest 1) that glucocorticoid regulation of phenylethanolamine N-methyltransferase activity occurs largely independent of gene expression; 2) that glucocorticoid effects on enzyme activity are primarily indirect, probably through cosubstrate regulation and/or enzyme stabilization; and 3) that these effects are not mediated via a classical (type II) glucocorticoid receptor mechanism, given the high doses of dexamethasone and corticosterone required and the inability of RU28362 to mimic the effects of these less selective steroids.


[Efficacy of intravenous and per os propafenone in the ambulatory treatment of recent-onset atrial fibrillation].

Propafenone efficacy in conversion of atrial fibrillation to sinus rhythm has been well documented. In this study we considered propafenone efficacy according to a graduated protocol of administration. Forty-two patients with recent-onset atrial fibrillation, without left ventricular failure, ischemic symptoms and in absence of antiarrhythmical treatment, were treated according to the following protocol: propafenone 1 mg/kg i.v. (5 min) followed, in the non-responder patient group, by a second dose, 0.5 mg/kg i.v. (15 min). Patients with persistent atrial fibrillation received 900 mg/daily of propafenone per os, at home for two days. Thereafter, patients still not restored to sinus rhythm were considered non-responders. Patients who were converted to sinus rhythm received 450 mg daily of the drug (oral administration), at home, as antiarrhythmical prophylaxis, for three months. Thirty-nine patients were converted to sinus rhythm (92.8%), 24 of them after intravenous propafenone (57.2%), and the other 15 (35.6%) after oral administration of the drug. The average heart rate in patients not converted to sinus rhythm with intravenous propafenone was significantly reduced after drug administration, compared to basal values (from 136.4 +/- 18.1 to 107.1 +/- 17.6, p < 0.01), allowing home treatment. No major cardiac effects were observed after infusion, nor after oral administration of propafenone. During a three-month follow-up we observed 3 cases of relapsed atrial fibrillation and 2 discontinued treatments due to minor gastroenteric side effects. In conclusion, propafenone therapy in ambulatory regimen is safe and effective in patients with recent-onset atrial fibrillation. In many patients refractory to IV treatment, further therapeutic success may be achieved following oral propafenone administration.


[Ventricular late potentials in hypertrophic cardiomyopathy: personal contribution and analysis of the literature].

Patients with hypertrophic cardiomyopathy are at increased risk of sudden death. Recently it has been investigated whether late potentials can be useful markers of that risk in such patients, with discordant results. The aim of our study was to detect a correlation, if any, between late potentials, ventricular tachycardia and the hypertrophy extension. Twenty-five patients were enrolled, 19 males and 6 females, mean age 40.40 +/- 15.02 years. Each underwent 24h Holter monitoring, averaged ECG, M-Mode and 2-D Echo. The hypertrophy was considered extensive (septum and free wall) or non extensive (septum and/or apex). Late potentials of a mean duration of 37 +/- 14.83 ms were recorded in 5/7 patients with documented ventricular tachycardia vs in none of the non tachycardia group. Sensibility was 100%, specificity 71% and predictive value 100%. Late potentials were present in 8.3% of patients with non extensive and in 30.8% of patients with extensive hypertrophy (p = NS). From our data it seems that extensive hypertrophy is present in about half of patients with hypertrophic cardiomyopathy, and this roughly correlates with a more frequent ventricular tachycardia and with late potentials. Furthermore, late potentials are strictly related to the incidence of ventricular tachycardia in this disease, just as in ischemic heart disease or in idiopathic dilated cardiomyopathy. The small number of our cases may not be sufficient to reach a significant statistical correlation between late potentials and hypertrophy, but we believe that the trend is very promising.


[Drop in cardiovascular and coronary mortality in Lombardia, 1969-1987. Evaluation of reliability of the estimates and possible explaining hypothesis].

The results of the present analysis indicate, from 1969 to 1987, a sharp and stable decline in cardiovascular (CVD) mortality in Italians aged 35-74 years (37.6% in males 53.6% in females). These trends were responsible for consistent reductions of total mortality (27.5% and 38% in the two gender groups, respectively), and for the increase of life expectancy. The decrease involved the two major components of CVD mortality, i.e. coronary heart disease (CHD) (23% in males and 44% in females) and cerebrovascular diseases (Stroke) (42.6% in the former and 51% in latter gender group). All these mortality decrements have been higher in the Lombardia Region. Comparing age-adjusted mortality rates in 1968 and 1987, it was possible to estimate that 23,040 deaths were saved in one year among the residents of this northern part of Italy, and the decrease of CHD mortality was responsible for about 30% of the total national decrement of CHD deaths, within comparable age strata. This is attributable both to the higher rates registered at the beginning of the studied period, and to the sharper decline observed. The social impact, in terms of reduction of deaths, was prominent for males. Among the northern male population, the amount of prevented deaths due to CHD and Stroke was equivalent (2072 vs 2172). Data from a MONICA Collaborating Center, located in the region--Area Brianza--, allow us to estimate, for coronary diagnoses reported on death certificates in the 1980s, acceptable levels of accuracy (Cohen's Kappa of .35, with 99% CI .27-.43) and sensitivity (87%). In comparison with earlier estimates carried out in the late 1970s, it is possible to hypothesize an increase of sensitivity over time for certified myocardial infarction diagnoses, which could have contributed to the underestimation of the observed decrements. In dealing with estimates of the reasons for these declines, only suggestions could be addressed because results of specific and comprehensive studies are not presently available. By comparing MONICA data with the results obtained in earlier surveys, it is possible to estimate that about 20 to 30% of the CHD decline, which occurred in the Region, might be attributed to the decrease of in-hospital coronary case-fatality. Moreover, major coronary risk factors (total cholesterol, blood pressure and cigarette smoking) show parallel positive changes, but their contribution in predicting the CHD downfall is difficult to evaluate on the basis of existing data.(ABSTRACT TRUNCATED AT 400 WORDS)


[Left ventricular aneurysmectomy: technical evolution and results].

A critical review of surgical techniques for left ventricular aneurysm treatment, with reference to literature data and author's personal experience, is reported. Aneurysm plicatio, performed in 35 patients, was always associated to coronary artery bypass graft and carried out mainly in small aneurysms of the posterior wall. In the last years this technique has been used very rarely, due to papillary muscle damage risk. Aneurysmectomy by usual technique only partially eliminates the a-dyskinetic area and moreover determines a severe ventricular deformation due to the linear suture. At Verona hospital it was carried out in 175 patients, with an 8% operative mortality and a survival rate of 82% at 3 years and of 80% at 5 years. Aneurysmectomy with converging walls left ventricular reconstruction, as proposed by Jatene and modified by the author, allows complete aneurysm removal and assures a ventricular reconstruction closer to normal morphology. In the Verona experience with this technique, referring to 51 patients operated up to 1989, operative mortality was 3.9% with a 89.9% survival rate at 3 years. These improved clinical results are associated with the improvement of left ventricular function indexes: average ejection fraction from 28.2% preoperatively to 42% postoperatively; average end diastolic left ventricular pressure from 23.6 mmHg to 18 mmHg.


[Emergency surgery of acute coronary insufficiency].

In our centre, during the last five years, emergency operations (within 6 hours) and urgent operations (within 72 hours) have represented 1/4 of all coronary surgery. 295 patients (pts) have been operated on since 1972: of these, 279 with simple revascularization, 5 with combined major surgery, and 11 as a consequence of mechanical complications of acute myocardial infarction. These last were all in cardiogenic shock: the overall 30-day mortality rate was 5.4% (3.6% in those pts with simple revascularization, 20% in those with combined major surgery, and 45.4% in pts with cardiogenic shock). In the subgroup with simple revascularization, the incidence of non fatal perioperative acute myocardial infarction (AMI) was 4.7% in 253 pts with unstable angina, 52.2% in 23 pts with abrupt closure during coronary angioplasty, and obviously 100% in 3 pts surgically treated during evolving AMI. We were able to identify in the univariate analysis as the only 30-day risk mortality factors: 1) a reduced ejection fraction (< 30%) and 2) the combination with endarterectomy. Other factors (female sex, age > 70, severity of angina, diffuse coronary artery disease and more than 3 by pass grafts) have shown a tendency to increase the mortality rate without statistical significance. No deaths occurred in pts revascularized in emergency situations due to coronary angioplasty complications. In recent years emergency and urgent coronary surgical operations have been increasing, with an increase in pts with higher risk factors. In pts with simple revascularization, 30-day mortality and incidence of myocardial infarction are similar to those of elective surgery. In pts with abrupt closure as a consequence of coronary angioplasty the mortality rate seems very low, while the incidence of infarction remains extremely high. These observations have allowed the development of an integrated protocol of intervention in acute unstable coronary syndromes.


[Surgical indications and results of myocardial revascularization in complications of PTCA].

Acute coronary occlusion during PTCA represents a significant procedural complication occurring in approximately 4-5% of cases, most frequently because of coronary dissection, spasm, or thrombosis. In these cases the first step in the management of acute ischemia is 1) a brief evaluation of its hemodynamic consequences and 2) the assessment and treatment of its cause. Spasm and intracoronary thrombus formation are usually readily identifiable and treatable using intracoronary nitroglycerin and thrombolytic therapy. In our catheterization laboratory the current approach to occlusive coronary dissection is represented by the use of autoperfusion dilatation catheters and by stent application. The atherectomy devices and the laser "welding" of the dissected intimal segment represent other alternatives that are still under clinical evaluation in this particular setting. If coronary occlusion is refractory to these efforts and coronary blood flow is not reestablished rapidly, emergency coronary bypass surgery is required to salvage jeopardized myocardium. In this case myocardial ischemia may be lessened by the insertion of an intra-aortic balloon pump. In our experience, the incidence of death (4%) and myocardial infarction (37%) for emergency CABG after a failed angioplasty, is similar to that reported by other Authors. The duration of myocardial ischemia and the presence of cardiogenic shock before operation are the most important determinants of major complications such as death and acute myocardial infarction.


[Surgical treatment of diffuse coronary disease].

Considering the morphological aspects of diffuse coronary disease one must argue that, in their presence, myocardial revascularization can be performed only by coronary endarterectomy (EA), together with conventional bypass grafting. A variety of EA techniques ("blind" and "open" EA) are analyzed. Indications, long and short-term results (operative risks, symptomatic improvement, grafts patency) of each procedure are evaluated on the basis of the current experiences. We conclude that EA is a valuable complement to coronary artery bypass grafting which allows: a) a larger number of conventionally inoperable patients to benefit from the surgical treatment; b) more complete revascularization in patients with diffuse coronary disease.


[Repeat myocardial revascularization].

Eighty-two consecutive patients undergoing reoperation for coronary revascularization from January 1980 to November 1990 were reviewed to determine early and late results and predictors of survival. Seventy patients were male and 12 female; age ranged from 36 to 75 years (mean 56.4 +/- 8.1). All were symptomatic for angina. The mean interval between first and second operation was 62.8 +/- 47.8 months (range 1 to 220 months). Angiographic indications for reoperation were: graft failure (34.1%), progression of atherosclerosis in the native coronary circulation (6.1%) and combination of the two (59.8%). Mean ejection fraction was 45.9 +/- 10.2 (range 11 to 67). Surgical indication was elective in 79.3%, urgent in 14.6% and emergent in 6.1%; 199 grafts were performed (2.4 +/- 1 grafts/patient). Hospital mortality was 6.1% (5 cases). Late mortality was 5.2% (4 cases). Actuarial survival rate (including hospital mortality) was 87.9% at 3, 5 and 10 years. Multivariate analysis identified left main stenosis (p = 0.00001), family history of coronary disease (p = 0.003), urgent/emergency operation (p = 0.015) as predictors of increased in-hospital mortality; postoperative myocardial infarction (p = 0.002) and preoperative heart failure (p = 0.01) as predictors of increased late mortality. Follow-up of in-hospital survivors (mean interval 42.7 +/- 25.8 months, range 3 to 120 months) documented 27 cardiac major events (other than death) in 24 patients (32.9%). Actuarial rates of freedom from major cardiac events were 70%, 52.9% and 48.1% at 3, 5 and 10 years respectively. Multivariate analysis identified preoperative ejection fraction (p = 0.01) as predictor of recurrence of angina and preoperative heart failure (p = 0.02) as predictor of occurrence of cardiac major events.


[Surgery of refractory ischemic arrhythmia].

Since June 1980, 138 patients have undergone surgical treatment for refractory ventricular tachycardia due to ischemic heart disease. Electrically guided surgical ablation (EGSA) of the focus was performed in 117 patients, while 14 patients underwent application of automatic implantable cardioverter-defibrillator (AICD), and 8 patients underwent heart transplantation. During the whole period considered, among the EGSA patients an operative mortality of 13 patients was observed (11.4%), with a late mortality of another 14 patients (13.4%). Two early and six late recurrences were described, and 4 cases of sudden or unexplained death, with 2 cases clearly due to an arrhythmic event. Multivariate analysis showed preoperative ejection fraction lower than 25% as a powerful predictor of early mortality (32% vs 0%). Actuarial survival rate of patients with LVEF lower than 25% was 67 +/- 12% vs 95 +/- 2% at one year and 37 +/- 25% vs 94 +/- 8% at 8 years. A high operative mortality was then observed in patients who underwent aneurysmectomy alone or visually guided procedures as compared to electrically guided procedures (75% or 3 deaths out of 4 patients vs 8.5% or 10 out of 113 patients, respectively). Patients who received an AICD with or without associated procedures showed 1 case of in-hospital mortality and no late mortality; in 6 patients at least one shock was delivered; in two patients the AICD was implanted during an EGSA procedure, due to multiple or difficult origins of the arrhythmias. Of patients who underwent heart transplantation one case of later mortality was observed due to malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)


[Ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension].

High resolution ultrasonography allows the accurate and reproducible measurement of thickness and lumen diameter of carotid arteries. We investigated Common carotid (CCA) and bifurcation intima-media thickness in 40 hypertensive patients, 20 without left ventricular hypertrophy (LVH) (age 42 +/- 10 years) and 20 with LVH (age 44 +/- 12 years), all free from other important cardiovascular risk factors. Both carotid axes were scanned from different views (anterior, lateral, posterior) on traversal and longitudinal section, using a high resolution steerable (HRS) 5.0 MHz linear array. Carotid diameter and thickness from longitudinal section were measured. CCA parameters were taken 20 mm caudally to flow divider. Using the B-mode as a guide we assessed LVH presence with M-mode technique when left ventricular mass index (LVMI) > or = 135 g/m2 for men and > or = 110 g/m2 for women. In hypertensive patients with LVH, left ventricular mass was significantly higher than in those without LVH (156 +/- 38 vs 98 +/- 10 g/m2, p < 0.01). Even blood pressure was significantly higher in hypertrophic group (172 +/- 21/108 +/- 9 vs 158 +/- 11/99 +/- 12 mmHg, p < 0.01), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness scanned in both CCA and bifurcation resulted significantly higher in hypertensives with LVH (CCA: 0.85 +/- 0.02 mm vs 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 mm vs 0.70 +/- 0.03 mm, p < 0.01). We also noticed a statistically significant correlation between carotid wall thickness and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)


[Complications and sequelae of cardiac electrostimulation in children. Our experience with 47 children].

Permanent cardiac pacing is now easily feasible in children and even in small infants, but the long-term results of this procedure are not well known. We analyzed our experience to determine the morbidity of pacing in children. Over the past 10 years, 47 pediatric patients (pts) required pacemaker implantation in our institution. The mean age was 8.3 +/- 4 years (1 day-17 years) and mean body weight was 23 +/- 14 Kg (2.2-60 Kg). 25 pts had heart disease. 40 children had an A-V block (congenital in 22 cases, post-operative in 17 pts, and secondary to a systemic disease in 1 case); 7 pts had a sick sinus syndrome, primitive in 4 and postoperative in 3 cases. The first pacemaker implantation was epicardial in 17 and transvenous in 30 pts. The pacing was single-chamber in 45 pts (VVI 32, VVIr 7, AAI 5, AAIr 1) and dual-chamber in 2 pts (DDD 1, VDD 1). Two newborns, both with a congenital A-V block and severe heart failure, died in the first hours after epicardial pacing. Two other children, both with congenital heart disease, died during follow-up, but the death was not pacemaker-related. Finally, two children were lost to follow-up. The mean follow-up of the 41 remaining pts was 5.2 +/- 3.5 years (4 months-10 years). Twelve children (29%) required 19 implant revisions and the causes were: lead fracture (26%), rising stimulation threshold (26%), growth problems (21%), erosion and/or pocket infection (21%). Revisions were more common in epicardial (52%) than in endocardial (22%) implantation.(ABSTRACT TRUNCATED AT 250 WORDS)


[Determination of prevalence and control level of hypertension in the community: Hypertension Management Audit Project--Vicenza].

As a part of the "Hypertension Management Audit Project" a random sample of 4070 subjects was drawn from the population aged 35-64 living in the city of Vicenza, in order to assess the prevalence and the level of control of hypertension in the community. 2854 (70.1%) were screened in the first step of the survey. Two blood pressure (BP) reading, height and weight measurements were performed and a short questionnaire filled in. Systolic BP (SBP) and diastolic BP (DBP) were (mean and 95% confidence interval) 143.7 (142.6-144.7) and 88.3 (87.7-88.8) mmHg in males; 137.8 (136.8-138.8) and 84.9 (84.5-85.5) mmHg in females, respectively. The BP value corresponding to the 95 degrees percentile of the cumulative distribution of BP was 180 mmHg for SBP and 105 mmHg for DBP in males; 173 mmHg for SBP and 100 mmHg for DBP in females. Systo-diastolic hypertension was present in 12.3% of the screened population; isolated diastolic hypertension in 9.1%; isolated systolic hypertension in 5.3%; borderline hypertension in 31.6%; severe hypertension (DBP > or = 115 mmHg) was present in 1.9% of females and in 2.2% of males. Prevalence in males was significantly higher with respect to females in all three categories of defined hypertension, but not in borderline hypertension. The second step of the survey involved 849 subjects (29.7% of the screened population) who completed two re-examinations because at the screening they had: 1) history of high BP; 2) BP > or = 160/95 mmHg; 3) ongoing antihypertensive treatment. At the end of the survey, 772 of these subjects (91%) were confirmed as hypertensives (mean BP of six readings > or = 140/90 mmHg and/or taking antihypertensive drugs). Patients aware of their high BP were 78.8%; aware and treated 51.0%; treated and controlled (BP < 140/90 mmHg) 19.1%. All indices of control were significantly higher in female with respect to male patients. Treated patients were significantly older than untreated patients; treated females had significantly lower BP than treated males, whereas no difference was detected between untreated patients; patients unaware of high BP had the highest BP values if compared to treated and untreated patients. This survey reveals a high prevalence of hypertension in the adult population of the city of Vicenza; quality of control shows a moderate improvement if compared to previous studies carried out in our country.


[Anatomo-functional study of non-rheumatic mitral insufficiency with transesophageal echocardiography].

Reconstruction surgery of the mitral valve has become an alternative to mitral replacement in patients with pure mitral regurgitation. Preoperative assessment of the anatomic and functional aspects of the valvular lesion is of the utmost importance in conservative surgery. Transesophageal echocardiography is a new approach to investigating the mitral valve, and our study was undertaken with the purpose of determining its importance in the exploration of mitral regurgitation of non-rheumatic origin. Subjects included were twenty patients with pure and isolated mitral regurgitation (MR): 14 males and 6 females with an average age of 47 +/- 13 years. All the patients underwent a first transesophageal 2D and color Doppler echocardiographic examination, and 5 of them underwent a second one during cardiovascular surgery. Mitral anulus diameter, mitral valve cordae tendinae status, valvular leaflet length and coaptation were examined and color Doppler regurgitation jet area was measured. Mitral anulus diameter was 40.2 +/- 8.06 mm (diastolic) and 41.9 +/- 8.53 mm (systolic) and was above the values considered to be normal. Anterior leaflet length was 30.8 +/- 3.12 mm and posterior leaflet length was 22.9 +/- 4.74 mm; regurgitation jet area was between 1.2 cm2 and 13.52 cm2 with an average of 5.44 cm2. In the group with MR of mixomatous origin, systolic anulus diameter showed a linear correlation with regurgitation jet area (r = 0.79). In the 6 patients who underwent cardiac catheterization, angiographic semiquantitative evaluation of the MR confirmed that based on color Doppler jet area. In all twenty patients transesophageal echocardiography enabled us to identify the mechanism responsible for mitral insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)


[Regression of left ventricular hypertrophy in obese hypertensive patients treated with diet and pharmacologic therapy].

Thirty-five obese (Body Mass Index: BMI > 30) hypertensive (diastolic blood pressure > 100 mmHg) patients were studied for 6 months. 18 patients (10 males, mean age 52 +/- 6 years) were treated with captopril 50 mg b.i.d. (Group 1); 17 patients, matched by age, sex and BMI were treated with captopril 50 mg b.i.d. and hypocaloric diet (Group 2). During follow-up a good control of blood pressure levels (< 150/90 mmHg) and a significant reduction in body weight (> 10%) were achieved in all patients of Group 2. Left heart anatomy was accessed by 2D guided M-mode echocardiogram before starting treatment and after 6 months. In Group 1 Interventricular Septal Thickness (ST), Posterior Wall Thickness (PWT) and Left Ventricular Mass (LVM) decreased significantly (p < 0.01). In Group 2 not only ST, PWT and LVM decreased significantly (p < 0.01 for ST and PWT, p < 0.001 for LVM), but also left atrial dimension (p < 0.05) and left ventricular diastolic dimension (p < 0.01). The percent reduction in AD, LVDD and LVM was significantly higher (p < 0.01) in Group 2. In obese hypertensives relevant weight loss can improve the effect of captopril treatment on left ventricular hypertrophy; the decrease of AD and LVDD is probably secondary to a reduction of the volume overload present in obese patients.


Methodology of baroreflex testing.

Recent clinical data have generated fresh interest in the assessment of baroreflex sensitivity, largely because of the relationship between this parameter and prognosis after a myocardial infarction. The present article reviews and discusses some of the methodologies currently used for the determination of baroreflex sensitivity. The Neck Chamber involves stimulation of the carotid baroreceptors by either augmenting or decreasing pressure at the level of the neck. The main advantage of this technique is to allow the simultaneous measurement of changes in heart rate and in the peripheral resistances. Another advantage is represented by the fact that no drugs are necessary for this type of study. On the other hand, this procedure modifies autonomic influences in several receptors areas while the stimulus is acting only at the carotid level; as a result of the baroreceptor activation or deactivation, this will produce complex and not uniform afferent information from receptors that are exposed to mechanical stimuli of opposite direction. In addition, it is difficult to quantify the pressure transmitted to the baroreceptors located in the carotid wall. The use of vasoactive substances, usually phenylephrine or nitroglycerin, produces a brisk change in pressure which is then linearly correlated with the attendant changes in the R-R interval to obtain a "baroreflex slope". The first concern with vasoactive drugs is that they act also on smooth muscle in the carotid sinus wall and might thereby interfere with the mechanical effects on the baroreceptors. The second is that peripheral resistance cannot be calculated at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)


Power spectral analysis of RR variability.

The analysis of beat-to-beat spontaneous oscillations of heart rate variability is a recent and noninvasive approach capable of providing important information on neural mechanisms controlling cardiovascular function. In particular, with spectral analysis of RR variability, two major components can be detected at low (LF, approximately 0.1 Hz) and high (HF, approximately 0.25 Hz) frequency. They have been demonstrated to be appropriate indices of, respectively, sympathetic and parasympathetic modulations of heart period. In control subjects, at rest, LF is slightly predominant over HF. In post myocardial infarction patients there is a predominant LF and a diminished HF that suggests an alteration of sympatho-vagal balance with a predominance of sympathetic tone. This approach, by providing indices of sympathetic and vagal neural regulatory outflows, appears adequate to evaluate several pathophysiological conditions such as ischemic heart disease, hypertension or congestive heart failure, which are characterized by important alterations of neural regulatory mechanisms.


The neck chamber technique.

Since the first description of the neck chamber technique for stimulating carotid baroreceptors by Ernsting and Parry in 1957, a number of different neck collars have been realized, among which the simplified version devised by Eckberg and coworkers in 1975 and the neck chamber described by Ludbrook and coworkers in our Institute in 1977. At variance with Eckberg's type, the "Milan neck chamber" completely surrounds the neck and allows the application of both positive and negative pressures to the neck by means of a system of double rubber valves that prevents air leakage from the chamber. The main advantage of this technique, as compared to infusion of vasoactive drugs, is the possibility it offers to study baroreflex control not only of heart rate, but also of peripheral resistance and blood pressure through neck chamber induced changes in carotid transmural pressure. In recent years a systematic evaluation of the neck chamber technique has allowed to clarify the following issues: 1) application of positive pressure to the neck, although increasing internal jugular venous pressure and thereby reducing the pressure gradient from the arterial versus the venous side of head circulation, does not reduce cerebral blood flow; 2) changes in pressure within the neck chamber do not seem to reduce blood flow to the carotid bodies, at least to a degree which might lead to chemoreceptor stimulation; 3) there is a linear relation between changes in neck chamber pressure and changes in tissue pressure adjacent to the carotid sinus. The transmission of pressure to pericarotid tissues is complex, however.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical assessment of respiratory sinus arrhythmia by computerized analysis of RR interval and respiration.

Heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) are often considered as interchangeable terms. However, the application of power spectral analysis to describe spontaneous fluctuations in heart period has clearly shown that RSA is only a part of HRV, and that in specific situations their respective patterns may diverge. In order to quantify the RSA we have used a mathematical method based on combined spectral analysis of respiration and RR interval (cross-correlation function), and evaluated its performance in terms of reproducibility, sensitivity to parasympathetic withdrawal and in clinical evaluation of autonomic function. Compared to other indices of HRV the cross-correlation between RR interval and respiration showed a greater sensitivity to parasympathetic withdrawal, better reproducibility and a high sensitivity in detecting autonomic dysfunction in diabetic patients. These findings suggest that specific indices of RSA, such as the cross-correlation, can be a valid tool for the diagnostic approach to cardiac autonomic dysfunction.


[Lack of tolerance after administration of delayed-action isosorbide-5-mononitrate for 3 days in patients with exercise-induced silent ischemia: control with placebo].

In order to assess the development of tolerance we analyzed in a placebo-controlled study the effect of monotherapy with isosorbide-5-mononitrate (IS-5-MN) 60 mg in a controlled release formulation (Durules) once-a-day. The IS-5-MN was evaluated after the first dose and after once-a-day therapy for three days in 11 ambulatory patients (10 males, 1 female, aged 54 +/- 9 years) with stable exercise-induced silent myocardial ischaemia and significant coronary stenoses. The drug was given at 8 o'clock in the morning, and a bicycle ergometer exercise test was performed after 4 hours. The ST segment depression was evaluated by a computer-assisted system. Standing blood pressure decreased during all three periods of active treatment with IS-5-MN, (in comparison with placebo p < 0.001 and p < 0.01, p < 0.01 respectively). Heart rate did not change significantly. Compared with placebo baseline values, ischaemic threshold increased during the first day of treatment (188 sec, p < 0.0001 at 4 hours), and to a lesser extent both in second (103 sec, p < 0.003) and third day (116 sec, p < 0.003). The total exercise time increased during all three days of active therapy but significantly so only during the first day. The exercise stress test performed in the 5th day during placebo demonstrated a high reproducibility of ischaemic-threshold (235 vs 241 sec, p: ns), implying that the improvement during the active treatment with IS-5-MN was not due to a "training effect". Headache in 2 patients was the only significant side-effect.(ABSTRACT TRUNCATED AT 250 WORDS)


[Perfusion catheter and cardio-pulmonary support standby: organizational strategy for high risk PTCA. Description of a case treated successfully].

The organizational strategy used in a high risk Coronary Angioplasty procedure is discussed. The attempted vessel was a severely stenosed Right Coronary Artery in a patient who had undergone triple graft, with residual obstruction of Left Main Artery and only one patent venous graft on a marginal branch of the Circumflex artery. The procedure was performed using a Stack type autoperfusion balloon angioplasty catheter, with a Cardiopulmonary Support System held in standby.


[Sepsis and endocarditis: two rare complications following pacemaker implantation. Description of a case and review of the literature].

A case of Staphylococcus aureus tricuspid valve endocarditis in a patient with permanent transvenous VVI pacemaker and recurrent febrile episodes is described. Medical treatment was not effective, and only with surgical removal of the lead was the infection successfully treated.


Ischemic modulation of myocardial innervation.

This article focuses on the interplay existing between the autonomic nervous system and the myocardium, with novel observations related to arrhythmogenesis. Myocardial ischemia and infarction produce an efferent denervation involving both limbs of the autonomic nervous system. As a consequence of the sympathetic denervation, the myocardial norepinephrine content is reduced to a major extent. As a logical consequence, this is followed by the phenomenon called "denervation supersensitivity", i.e. the tissue deprived of its nerve supply responds to the neural mediator in an exaggerated fashion. This is manifested by an exaggerated shortening of the effective refractory period during infusion of norepinephrine and by increased propensity for arrhythmias. With time, denervation is followed by reinnervation. An interesting counterpart of these findings is the possibility to document in patients after myocardial infarction if denervation has occurred using the MIBG technique. Not only efferent but also afferent denervation does occur and this might be involved in painless ischemia. In another series of studies we have provided the evidence that the pericardium is not a mere inert sac but it actively acts as a functional membrane. Pericardial prostaglandins released into the pericardial fluid alter electrophysiologic properties by modulating mostly the sympathetic effects; this may serve as a physiologic negative feedback control mechanism regulating sympathetic effects on the heart contributing to prevention of ischemic arrhythmias.


Baroreceptor reflexes and sudden cardiac death: experimental findings and background.

The identification of subjects at high risk for sudden cardiac death is a key factor for an adequate preventive strategy. Relevant animal models may provide both a better understanding of the pathophysiologic mechanism involved and suggestions for a more precise risk stratification. Vagal hyperactivity is generally beneficial in the setting of acute myocardial ischemia. In a conscious animal model for sudden cardiac death, electric vagal stimulation markedly reduces the incidence of ventricular fibrillation (VF) in a high risk subgroup, whereas muscarinic blockade increases malignant arrhythmias in low risk animals. Among 192 dogs, those that develop VF during an episode of acute myocardial ischemia one month after myocardial infarction, have a significantly lower baroreceptor reflex sensitivity, compared to the survivors (9.1 +/- 6.0 vs 17.7 +/- 6.5 msec/mmHg, p < 0.0001). Furthermore, the analysis of vagal reflexes may identify high risk animals also before myocardial infarction. Therefore, the experimental studies indicate that the analysis of baroreceptor reflexes may be a powerful tool in the stratification of risk for sudden cardiac death.


Myocardial infarction and baroreflex sensitivity. Clinical studies.

Based on solid experimental evidence the concept has emerged that analysis of autonomic reflexes, and specifically of baroreceptive reflexes, might contribute to the identification of high risk subgroups in the post myocardial infarction phase. Accordingly, we brought this concept to clinical fruition and have performed the first clinical study to investigate the potential prognostic value of baroreflex sensitivity. The present article reviews those clinical results which indicate an almost 15 times greater risk for cardiac mortality among the patients with depressed baroreflex sensitivity. Baroreflex sensitivity has also been correlated with heart rate variability and it was found that the degree of correlation is relatively weak and such that it is not possible to predict one measure from the other. Thus, these two autonomic markers are not redundant. Among the various possibilities to induce favorable alterations in the autonomic balance, our group has selected and analyzed exercise training and the chronic administration of beta-blocking agents. Exercise training, examined in a case-control study involving 70 patients, was found to increase baroreflex sensitivity by 30%. Beta-blockers were found to augment baroreflex sensitivity in 40% of the patients tested. As a logical evolution of these studies we have initiated a large prospective collaborative study destined to enroll 1200 post myocardial infarction patients and to assess the prognostic value of baroreflex sensitivity, of heart rate variability, and of traditional markers such as left ventricular ejection fraction and late potentials.


Heart rate variability and the onset of tachyarrhythmias.

The autonomic nervous system plays an important role in the genesis of cardiac arrhythmias but the precise definition of this role is quite complex. The fluctuations of the heart rate may provide useful information about the balance of the autonomic nervous system. However, one obvious limitation is represented by extrapolating to the ventricle events which occur at the sinus node level. It has been clearly documented that atrial fibrillation of vagal origin is preceded by a progressive decrease in heart rate. On the other hand, ventricular arrhythmias of adrenergic origin are preceded by progressive heart rate acceleration and by diminution of vagally mediated short term changes. The absolute value in heart rate is less important than the actual trend in allowing inferences on the relative sympathetic or vagal predominance. A better understanding of the changes in the autonomic balance will provide a key for the mechanisms underlying several clinical events.


[Coronary angioplasty in postinfarct angina].

The recurrence of transient myocardial ischemia is a frequent event in the course of acute myocardial infarction. Postinfarction angina develops more frequently after a non-Q wave infarction, and after effective thrombolysis; when uncontrolled by standard medical treatment, it is associated with an increased incidence of unfavorable cardiac events. Therapeutic strategies involve aggressive medical therapy, frequent use of early angiography, and mechanical coronary revascularization with bypass surgery or transluminal coronary angioplasty (PTCA). We retrospectively examined 68 consecutive patients treated with PTCA for postinfarction angina. Of the whole, 36 (53%) had sustained a non-Q wave infarction; 29 (43%) had been treated with thrombolysis in the acute phase. Ischemia was in the infarction zone in 94% of cases; mean EF was 61.5 +/- 12%, and in 18 cases EF was < 55%. In 7 cases two arteries were dilated. There were no deaths related to the procedure. The overall success rate was 91.2%. Major complications occurred in 2 cases (1 acute occlusion with reinfarction, 1 major dissection requiring emergency surgery). The results are analyzed according to the time interval between index infarction and PTCA. In 28 cases (Group A) PTCA was performed within 30 days due to medically refractory symptomatology; in 40 cases (Group B) PTCA was postponed to beyond 30 days from infarction. In Group A involvement of the left anterior descending coronary artery was more frequent (75% of cases vs 40%; p = 0.009). The success rate in Group A was slightly lower than for Group B (85.7% vs 95%); the incidence of complications was higher (7.1% vs 0%), although not statistically different. At 6 month follow-up a restenosis was found in 10 cases (16% of successful PTCAs, 21% of angiographic controls). We conclude that for patients with postinfarction angina, selected for a suitable coronary anatomy, PTCA is an effective therapeutic option, with a high success rate, low immediate morbidity, and good mid-term results. The risk of intraprocedural complications appears only slightly higher for patients with unstable symptoms, who undergo PTCA earlier after infarction.


[The electrocardiographic anomalies and 2D-echocardiographic findings during the recovery phase of the stress test in the postinfarct patient].

The appearance or the increase of repolarization abnormalities in the EKG during post exercise (ET) recovery phase (R) is considered a marker of ischemia. In order to evaluate the real meaning of these changes we compared the EKG data with eventual modifications of left ventricular kinesis analyzed by 2D-ECHO. 10 male patients with previous myocardial infarction, mean age 50 +/- 4.8 y, underwent exercise testing on a treadmill (Bruce's protocol) and continuous 2D-ECHO observation from the end of exercise along the whole R. Patients were divided in two groups: Group A (6 patients) and Group B (4 patients), all free of symptoms. Group A showed ischemic EKG markers during exercise which increased during R; Group B showed ischemic EKG markers only during R. The 2D-ECHO showed in Group A an impairment of left ventricular kinesis at peak exercise without increase or extension during R (WMSI at rest 1.32; peak ET 1.60; R 1.60); in Group B the kinetic alterations appeared only in R (WMSI at rest 1.33, peak ET 1.42; R 1.80), strictly related to EKG markers. The data suggest : 1) that the increase of EKG abnormalities already present during exercise do not seem to imply more severe ischemia; 2) that EKG changes appearing during R are markers of ischemia which occur in the R.


[Coronary angioplasty without surgical standby: a prospective study].

In 811 out of 1000 consecutive patients submitted to coronary angioplasty we elected not to arrange for surgical standby. All patients were informed, and accepted that in case of vessel occlusion an infarction might ensue, for which a conservative management was planned. This choice was made on the basis of a clinical and angiographic estimate of the possible consequences of vessel occlusion, or dictated by sound inoperability of the patient. Primary success was achieved in 700 patients (86%) and in 933/1026 lesions (91%). Fifty-six patients (6.9%) had an acute vessel occlusion (within 24 hours of the procedure), with Q or non Q-wave infarction in 24 cases (2.9% of patients). Emergency coronary stenting was performed in 9 patients. One patient had emergency bypass surgery 1 hour after the procedure, and another had urgent bypass surgery 24 hours after the procedure because of left main stem dissection: the former died despite surgery, the latter was discharged uneventfully. The remaining 7 in-hospital deaths (total mortality 1%) could not have been prevented by surgical standby: one patient died from electromechanical dissociation during the procedure, due to rupture of a ventricular pseudoaneurysm; another died after an uncomplicated procedure, due to an anaphylactic reaction to protamine; two others died suddenly 3 and 20 days, respectively, after a successful procedure; finally, three patients were "a priori" inoperable. Our data suggest that surgical standby is not necessary for a large number of angioplasty candidates, who can be identified on the basis of preliminary clinical and angiographic evidence.(ABSTRACT TRUNCATED AT 250 WORDS)


[Sotalol in the Wolff-Parkinson-White syndrome: an electrophysiological and clinical study].

Distinctly different from the other beta-blocking agents, sotalol prolongs action potential duration in myocardial and Purkinje fibers, and increases atrial as well as ventricular effective refractory periods. Similarly, antegrade and retrograde accessory pathway refractory periods are increased by sotalol. The electrophysiologic and clinical effects of sotalol were studied in 40 patients (31 male and 9 female, mean age 32 +/- 14 years) with Wolff-Parkinson-White Syndrome (WPW). All patients had disabling episodes of supraventricular tachyarrhythmias (ST). Of the 40 patients, 15 (37%) had spontaneous recurrence of paroxysmal supraventricular reciprocating tachycardia (PSRT), 14 (35%) of atrial fibrillation (AF) and 11 (28%) of both PSRT and AF. All of the patients were non responders to serial transesophageal electropharmacological tests using I C class drugs. Sotalol 252 +/- 73 mg daily was administered, and, in steady-state, a new transesophageal study (TS) was performed to observe the re-induction of PSRT and/or AF. 34 patients (85%) were responders to TS (noninducibility of ST, or nonsustained ST or AF inducibility with an increase of 30% in the minimum R-R interval between pre-excitated beats during AF) and the results were confirmed during a follow-up of 17 +/- 9 months. In the non-responder group (5 patients), a I C class drug was associated with sotalol. One patient, who was a "non responder" to sotalol, sotalol + I C class drug, and to amiodarone, underwent surgical therapy. In the 26 patients (65%) who had episodes of PSRT (37%) or episodes of PSRT and AF (28%), it was impossible to reinduce PSRT in 85% of the cases. AF was induced at baseline in all of the studied patients, but after sotalol administration in 15 patients, it was impossible to reinduce AF. The rate of induced AF decreased from 208 +/- 39 beats/min to 156 +/- 36 beats/min (p < 0.001). The mean shortest R-R interval between pre-excitated beats increased from 214 +/- 35 (baseline) to 293 +/- 97 msec (sotalol steady state) (p < 0.001). No side effects were observed. A significant prolongation (p < 0.001) of the QTc interval was observed in all the patients after sotalol administration (from 0.39 +/- 0.2 to 0.42 +/- 0.02 sec.). On the basis of our results, we may conclude that sotalol has a potent effect on the antegrade refractoriness of the anomalous pathway and, in WPW syndrome at risk, is also effective in patients who don't respond to I C class drugs.


[Paroxysmal atrial fibrillation in patients with chronic ischemic cardiopathy: a study of high-resolution atrial activation].

Patients with ischemic heart disease and episodes of paroxysmal atrial fibrillation are at major risk of stroke. In order to prevent such episodes, through the identification of patients prone to atrial fibrillation, we investigated the high-resolution atriogram of 65 patients with chronic ischemic heart disease, 54 male and 11 female, mean age 60.22 +/- 9.04 years. Based on previous documented episodes of atrial fibrillation, the patients were divided into two groups: group A, 45 males and 3 females, mean age 58.92 +/- 7.68 years, without atrial fibrillation; group B, 9 males and 8 females, mean age 63.88 +/- 11.6 years, with atrial fibrillation. High resolution atrial duration (100-300 Hz) in group B (with atrial fibrillation) was higher than in group A (without atrial fibrillation) (140.59 +/- 16.85 ms vs 121.77 +/- 11.27 ms, p < 0.001); Non filtered atrial duration (0-300 Hz) was not different between the two groups, A and B (118.54 +/- 10.96 ms vs 123.53 +/- 18.77 ms, p = NS); The prevalence of late atrial potentials was higher in group B than in group A (60.8% vs 7.1%, p < 0.001); No relation was observed between high resolution atriogram data and echocardiographic measurements; Sensibility was 82%, specificity 81%, and predictivity 60%. Data from our study show that high resolution electrocardiography is a valid tool for identifying patients prone to atrial fibrillation. Such patients can be identified by the presence of "late atrial potentials" that, like late ventricular potentials for ventricular tachycardia, are correlated with atrial fibrillation. Nevertheless, a larger cohort of patients is necessary to confirm these results.


[Persistent T-wave inversion in unstable angina: the correlation with the global and regional function of the left ventricle].

The correlation between persistent negative T wave on basal electrocardiogram and coronary anatomy or global and regional left ventricular function was investigated in 34 patients with unstable angina defined as new onset (< 2 months), crescendo or rest angina. The patients with history of previous myocardial infarction, pathological Q waves on electrocardiogram or documented elevation of CPK were excluded. Eighteen patients (group A) showed T wave inversion (> 1 mV) in at least two leads on the basal electrocardiogram, persisting for at least 48 hours before coronary arteriography. In 16 patients (group B) the basal electrocardiogram was normal. Left ventricular volumes and ejection fraction were calculated and the regional systolic wall motion was analyzed using the area method in the 30 degrees right anterior oblique view. Hypokinesis was defined as more than 2 standard deviation below the mean value calculated in 24 normal subjects. No difference was present for age (A: 61 +/- 9 vs B: 57 +/- 9 yrs) and sex distribution. Critical stenoses of at least one coronary artery was documented in all but one patient (in group B). The number of critical stenosis per patient was equal (1.8) in the two groups. Left main coronary artery showed narrowing > 50% in three patients of group A and in two patients of group B.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cardiologic emergencies: mortality and treatment. An analysis of 500 consecutive coronary events within the framework of the WHO-MONICA Project--Brianza Area. The Research Group of the WHO-MONICA Project--Brianza Area].

Recently, a decreasing trend in cardiovascular mortality, starting from 1976-78, has been observed in Italy, particularly in northern regions. In order to explore one possible cause of the phenomenon, a survey of acute coronary care has been performed in a sample area, with about one tenth of the population of Lombardy, the largest and most developed northern Italian region. The survey has been carried out within the framework of the WHO-MONICA project: the treatment of 500 consecutive suspected coronary events in the age group 25-64 years, has been examined according to the international protocol. The following items have been investigated: time between onset of symptoms and medical intervention; characteristics of initial care; cardiac arrest and cardiopulmonary resuscitation in or outside the hospital; intensive care unit admission and length of stay; type of treatment before, during and after the event. Marked improvements have been accomplished in managing cardiac emergency. They have reduced in-hospital coronary mortality by more than 50%. However, several problems were still present at the time of the study, 1986-87: a) only 52% of patients obtained assistance within 4 hours (Tab III); b) cardiac arrest was practically always fatal outside the hospital and in 75% of the cases inside (Tab V); c) essential drugs, e.g. beta-blockers, were not so widespread and substantially absent were angioplasty and coronary bypass surgery (Tab IX). It has been estimated that improving adherence to optimal therapeutic standards might save more than 700 lives a year in Lombardy in the age group 25-65 years.


[Pulmonary valve angioplasty via the jugular vein in a 73-year-old female patient].

Percutaneous balloon valvuloplasty was successfully performed in a 73-year-old woman with severe congestive heart failure due to severe calcific valvular pulmonary stenosis. An approach by right internal jugular vein was used for the procedure.


[Digestive cancers in France. Comparison of the incidence in 7 departments and estimation of incidence in the entire country of France].

Estimation of differences in the incidence of digestive cancers in France was made from incidence data coming from 7 French departments covered by population-based registries. For some localizations, such as cancer of the pancreas, incidence variations could be explained by differences in recording techniques. But geographic variations clearly appeared for digestive tract cancers: the incidence of esophageal cancer is 4 to 5 fold less in the departments of Tarn and Haute-Garonne than in the department of Calvados. Conversely, the incidence of colorectal cancer is lower in the department of Calvados than in the others. For the entire country, the estimated number of digestive cancers is 46,300 cases per year. This number represents a third of all cancers in males and a fourth in females. Colorectal cancer (25,700 cases per year) is the most frequent of all cancers in both sexes. Cancer of the stomach (8,200 cases per year) is the second digestive cancer, equal to esophageal cancer in males. The heavy burden of digestive cancers in public health is emphasized by our results. These results should lead our country to intensify research in the direction of primary and secondary prevention.


Antineutrophil cytoplasmic autoantibodies in inflammatory bowel diseases.

Antineutrophil cytoplasmic autoantibodies have been recently reported in sera from patients with inflammatory bowel disease. We report our experience based on 90 patients with ulcerative colitis, 148 patients with Crohn's disease, and 60 controls. Determination of antineutrophil cytoplasmic autoantibodies was performed by the indirect immunofluorescence technique on ethanol fixed leucocytes. The specificities for proteinase 3, myeloperoxidase, and lactoferrin were tested by enzyme-linked immunosorbent assay. Forty-three out of 90 (48%) patients with ulcerative colitis, 10 out of 148 (7%) patients with Crohn's disease, and none of controls were positive by indirect immunofluorescence technique. All patients but two with positive immunofluorescence exhibited a perinuclear staining pattern. Among patients with ulcerative colitis, there was no relationship between the presence of perinuclear antineutrophil cytoplasmic autoantibodies and disease location or activity. Seven out of 20 (35%) patients with ulcerative colitis who had a previous colectomy (including 1 with ileoanal anastomosis) had perinuclear antineutrophil cytoplasmic autoantibodies. Antineutrophil cytoplasmic autoantibody specificity was not directed against myeloperoxidase, proteinase 3 or lactoferrin in sera from patients with inflammatory bowel diseases. Inflammatory bowel diseases are associated with a new subset of antineutrophil cytoplasmic autoantibodies. Among patients with Crohn's disease and ulcerative colitis, the sensitivity and specificity of the presence of perinuclear antineutrophil cytoplasmic autoantibodies for ulcerative colitis was 46% and 93%, respectively. Their presence reinforces the likelihood of underlying immunologic dysregulation in ulcerative colitis. Identification of the autoantigen(s) to which these antibodies are directed might facilitate the understanding of inflammatory bowel disease pathophysiology.


[Digestive lymphomatous polyposis].

We report 7 prospectively followed cases of lymphomatous polyposis of the gastrointestinal tract. They were characterized by multiple polypoid lesions affecting several segments of the gastrointestinal tract always involving the colon and the rectum. An ileocecal mass was present in 4 cases. Regional lymph node involvement was constant. Peripheral lymphadenopathy was frequent (5 cases out of 7), as was other extra-digestive extension to the bone marrow (4 cases out of 7) and cavum (3 cases out of 7). The histopathological aspect was that of a small cleaved cells (working formulation) or centrocytic (Kiel classification) non-Hodgkin's lymphoma. The peculiar morphology and phenotype of the tumoral B-lymphocytes suggest their possible follicle marginal zone origin. Lymphomatous polyposis bore a rapidly fatal prognosis in every case (mean survival 20 months). This study of seven patients together with the 20 well-documented cases of the literature confirms the existence of lymphomatous polyposis as a distinctive clinicopathological entity among gastrointestinal non-Hodgkin's lymphoma.


[Seroepidemiology of hepatitis A in six departments in West-Central France in 1991].

Antibodies to hepatitis A virus were sought for among residents of 6 "départements" of West-Central France during a routine medical check up provided by the national health insurance system to all affiliated persons. Among them 5,641 subjects (aged 6 to 60) were randomly selected to a sample size of 256 +/- 15 male or female subjects for each five-year age group. Anti-HAV were detected in 51% of the screened population. The prevalence was less than 5% in the 6-15 age group and increased by successive steps to exceed 90% in the subjects over 50. The highest increase was observed between the 26-30 (39%) and the 31-35 (57%) age groups. This study confirms the influence of socio-economical factors on the anti-HAV prevalence rate. Factors such as profession or scholar education were previously known, but the housing conditions and especially the number of siblings were identified in our present report. In relation to this low prevalence of anti-HAV among young adults, one may fear an increase of overt hepatitis cases which are known to be more frequent in adults than in infants or children. Moreover any break in hygiene may expose the population to an epidemia. Only active immunization with a vaccine against hepatitis A could efficiently prevent these individual and community-related risks.


[Hemodynamic effects of the administration of terlipressin alone or combined with nitroglycerin in patients with cirrhosis].

Terlipressin (Glypressin), a synthetic analog of vasopressin, induces arteriolar vasoconstriction which causes both a portal hypotensive effect and certain side-effects on the systemic circulation (elevated arterial pressure and reduced cardiac output). The combination of nitroglycerin with terlipressin might accentuate the portal hypotensive effect and prevent the side-effects on the systemic circulation. The aim of this study was to examine the systemic and splanchnic hemodynamic responses to terlipressin administered alone or combined with nitroglycerin in patients with cirrhosis. Systemic and splanchnic hemodynamics were measured before and 1 h after a bolus of terlipressin (1 to 2 mg IV) given alone (n = 10) or in association with nitroglycerin infusion (25 micrograms/min, n = 9). Terlipressin alone significantly increased the arterial pressure by 21%, systemic vascular resistance by 60%, and significantly decreased cardiac output by 23%. The right atrial and pulmonary pressures significantly increased and the wedged hepatic venous pressure and hepatic venous pressure gradient significantly decreased by 8% and 16%, respectively. The combined therapy decreased the cardiac output by 20%, but did not significantly modify the other systemic and splanchnic hemodynamic values. No significant differences were found between terlipressin and the combined therapy concerning changes in wedged hepatic venous pressure or hepatic venous pressure gradient. We conclude that in patients with cirrhosis, nitroglycerin prevents the deleterious vasoconstrictor and vasopressor effects of terlipressin. However, the combined therapy, as terlipressin alone, decreases the cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of acute administration of acamprosate on the risk of encephalopathy and on arterial pressure in patients with alcoholic cirrhosis].

To evaluate the risk of hepatic encephalopathy and arterial hypotension in cirrhotic patients after acute administration of acamprosate, a GABA mimetic drug used in the weaned alcoholic, a randomized double-blind trial was conducted in 24 cirrhotic patients with low or moderate hepatic insufficiency (Pugh grade A or B). Twelve patients received 666 mg (2 tablets) of acamprosate and 12 received placebo. The 2 groups were similar before treatment, except for a male predominance in the acamprosate group. Tested parameters were the P100 latency of visual evoked potentials using a checkerboard pattern reversal as stimulus, the number connection test and the arterial blood pressure in upright and recumbent positions. The two first parameters were studied before and 2 hours after treatment. Blood pressure was recorded every half hour during 6 hours. No significant effect on the development of subclinical hepatic encephalopathy was noted. Nevertheless, even if some authors disagree with the GABA hypothesis of hepatic encephalopathy, it is possible that the dose was too low to induce subclinical hepatic encephalopathy. A study with more prolonged treatment could be necessary to be sure of the drug's safety in these patients. On the other hand, a transient decrease of diastolic arterial blood pressure was observed without significant systolic blood pressure modification. These results suggest that a moderate dose of acamprosate does not induce subclinical encephalopathy, but transient diastolic hypotension.


[Infection of ascitic fluid by perforation of a sclerodermic colon].

In progressive systemic scleroderma, a disease of protean manifestations, involvement of the gastrointestinal tract is noted infrequently in patients who are asymptomatic, and is rarely fatal. We report the case of a 65-year-old woman who was admitted for ascitis related to a non A, non B cirrhosis. The patient presented with bacterial peritonitis due to colonic perforation by fecal impaction associated with sclerodermic involvement. Pathologic study of the resected colon showed that the true muscularis was very atrophic and fibrotic, characteristic of scleroderma. To our knowledge, this cause of ascitic fluid infection has not been previously reported.


[Cystadenoma of the extrahepatic bile ducts: a rare cause of cholestasis].

We report the case of a 45-year-old woman who underwent laparotomy for obstructive jaundice due to an uncommon cystic tumor located in the porta hepatis. Histology of the resected specimen disclosed a cystadenoma of the common hepatic duct. A review of 20 reported cases shows that the preoperative diagnosis is uncommon; wide resection appears to be the treatment of choice since these lesions are susceptible of local recurrence and malignant change.


[Leiomyosarcoma of the inferior vena cava invading into the liver. Complete resection with venous reconstruction].

A case of leiomyosarcoma of the retrohepatic inferior vena cava associated with metastasis in the right liver lobe is reported. Resection included extended right hepatectomy, right nephrectomy, and tumor--containing inferior vena cava resection followed by polytetrafluoroethylene tube reconstruction. A comfortable survival was obtained before multifocal malignant spread led to death 42 months after surgery.


Acute abdomen of unknown origin: impact of CT on diagnosis and management.

A prospective study was performed including 40 patients with an acute abdominal syndrome presenting difficulties in defining the etiology. All patients underwent an emergency computed tomographic (CT) scan. The CT scan made the syndrome's diagnosis in 95% of cases and it permitted the detection of a lesion in 57.5% of cases. The diagnostic impact of CT scan was significant (p less than 0.01). The value and the specific contribution of CT in various diseases were analyzed. CT allowed appropriate therapeutic decisions in 95% of cases where clinical examination performance was positive in only 60% of cases. We had two negative CT results leading to an inappropriate therapeutic decision; it consisted of two cases of undiagnosed appendicitis. CT modified the primary therapeutic strategy in 30% of cases and avoided seven laparotomies.


Graded compression sonography of abdominal neoplasms mimicking acute appendicitis.

Over a 3-year period nine patients (mean age of 43 years) with acute abdominal pain and unsuspected abdominal neoplasms were referred for graded compression sonography to rule out appendicitis. Six of the nine patients had right lower quadrant neoplasms involving the cecum, terminal ileum, iliacus muscle, or iliac lymph nodes. However, in three patients neoplasm was noted outside the right iliac fossa involving the liver, right kidney, and upper abdominal mesentery. This study underscores the fact that in patients without sonographic evidence of acute appendicitis, a survey of the upper abdomen and right flank should routinely be performed in addition to scanning the right iliac fossa and pelvis. In patients more than 50 years of age neoplasm must also be kept in mind in the differential diagnosis of appendicitis.


Fast spin-echo imaging of the abdomen during breath-holding: an alternative to RASE and other fast imaging techniques.

We have developed a rapidly acquired T1-weighted spin-echo pulse sequence that uses gradient echo-like parameters of TR 70 ms, TE 10 ms, NEX-1 (SE 70/10/1) with large pulse angles, and presaturation. This sequence yields two images of the abdomen during a comfortable breath-hold of 9 s. Preliminary phantom studies with this sequence demonstrated that peak signal-to-noise ratios occurred at pulse angles of 120 degrees and 135 degrees. Compared to this rapidly acquired sequence, a conventional T1-weighted spin-echo sequence of TR 140 ms, TE 10 ms, NEX-4 demonstrated 2.8 times the signal-to-noise ratio, 2.6 times the liver-spleen contrast-to-noise ratio but only 1.6 times the contrast-to-artifact ratio. When normalized for the imaging time, however, there was little difference in the signal-to-noise and contrast-to-noise ratios, although the SE 70/10/1 demonstrated 2.0 times the contrast-to-artifact ratio. We conclude that for abdominal imaging the SE 70/10/1 is an excellent alternative to RASE and other fast imaging techniques, and, although there are inherently low signal-to-noise ratios, it may be particularly useful when coupled with a paramagnetic contrast agent.


Gd-DTPA as an intestinal contrast agent for MR imaging of the lower abdomen: phase III clinical trial.

Thirty-one patients were investigated with magnetic resonance (MR) imaging of the lower abdomen before and after the administration of gadopentetate dimeglumine (Gd-DTPA) solution per os or per rectum or from both routes for the opacification of the intestinal tract. The parameters evaluated were: (a) contrast medium distribution, (b) degree of filling of the bowel lumen, (c) contrast between the bowel lumen and the surrounding normal or pathological structures, and (d) whether the administration of the contrast agent improved the diagnostic ability of MR compared to computed tomography (CT) or plain MR of the same region. Gd-DTPA, at a concentration of 1 mmol/L, produced a positive signal irrespective of its dilution in the bowel and good contrast between the bowel lumen and the adjacent tissues or any possible pathological lesions. From the diagnostic point of view, after the administration of contrast medium, MR is comparable to CT and much superior to plain MR. It is concluded that opacification of the bowel with Gd-DTPA solution will improve the diagnostic yield of MR imaging of the lower abdomen.


Assessment of distant metastases with ultrasound-guided fine-needle aspiration biopsy and cytologic study in carcinoma of the esophagus and gastroesophageal junction.

The use of ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) for the assessment of distant metastases was prospectively studied in 135 consecutive patients with carcinoma of the esophagus and gastroesophageal junction. Patients with accessible lesions on US and computed tomographic (CT) studies of the supraclavicular regions and the abdomen underwent US-guided FNAB. In patients with multiple lesions biopsies were preferentially performed on enlarged supraclavicular nodes. Forty-nine patients underwent US-guided FNABs of 53 lesions. A cytologic diagnosis was established in 46 of 53 (87%) biopsies. Seven of 53 (13%) biopsies were nondiagnostic. Distant metastases were diagnosed by means of cytologic study in 33 of 135 (24%) patients. Supraclavicular metastases were diagnosed in 22 patients and abdominal metastases were diagnosed in 12 patients, including one patient who also had supraclavicular metastases. US-guided FNAB can improve the selection of patients for surgical and nonsurgical treatment by diagnosing distant metastases in an important number of patients.


Inflammatory myofibrohistiocytic proliferation presenting as giant gastric pseudotumor.

A 5-year-old boy presented with refractory microcytic anemia, growth failure, and markedly elevated sedimentation rate. Computed tomographic (CT) and upper gastrointestinal study disclosed an ulcerated 9-cm large gastric mass, which proved to be an inflammatory myofibrohistiocytic proliferation (IMP). The characteristic clinical and radiologic features of this rare entity are herein reviewed.


Embolotherapy of massive duodenal hemorrhage.

Eleven patients with massive duodenal hemorrhage were treated by emergent embolization. Bleeding originated from duodenal ulcer in three patients, from duodenal tumor in one, from ruptured pancreaticoduodenal artery pseudoaneurysm in three, and from ruptured gastroduodenal artery pseudoaneurysm in four. Complete hemostasis was obtained immediately after embolotherapy in all cases. Three of these patients died during the hospitalization period, one of whom from duodenal infarction and pancreas necrosis induced by embolization. In three patients with duodenal ulcer, complete hemostasis was obtained only by the gastroduodenal artery embolization with Gelfoam particles. Seven patients with pseudoaneurysms of the gastroduodenal artery or its branches required not only blockage of blood flow from the celiac artery but also the superior mesenteric artery for complete hemostasis. Therefore, in patients presenting with duodenal hemorrhage, the possibility of dual blood supply to the duodenum should be considered. Emergent embolization represents a useful alternative to surgery for massive duodenal hemorrhage, but it carries a risk of complications in patients with previous gastroduodenal surgery or significant visceral atherosclerosis.


Successful arterial embolization of arteriovenous fistula in the portal circulation.

We successfully performed arterial embolization of an arteriovenous fistula between the left gastric artery and vein. The increased blood flow in the portal vein via the left gastric vein and the arteriovenous fistula induced severe portal hypertension. After obliteration of the left gastric artery, the arteriovenous fistula was not opacified on angiography and the portal hypertension improved.


Radiographic features in ischemic jejunoileitis: serial changes and comparison with pathologic findings.

Serial radiographic examinations of the small intestine, including double-contrast studies, were performed in 13 patients with ischemic jejunoileitis, nine with the stricturing form and four with the transient form. Thumbprinting was observed in five (38%) patients and thickening of the folds in four (31%) at the acute stage of the disease. Tubular narrowing with irregular contours and dilated proximal bowel was observed in six (46%) patients and appeared on day 27 or later. Pathologic findings of the resected specimen in eight patients with the stricturing form revealed annular stricture with relatively shallow ulcers; the irregular contours of the tubular narrowing on radiographs were consistent with a granular or nodular appearance and/or multiple fissures on pathologic study. Eccentric deformity and sacculation were demonstrated in only one patient with the stricturing form. In addition, double-contrast study revealed small ulcers in three (23%) patients. Our results indicate that radiographic findings accurately reflect the clinical course and pathologic findings in this disease.


Retractile mesenteritis with colon and retroperitoneum involvement: CT findings.

We report a case of retractile mesenteritis which involved the rectosigmoid colon and extended into the retroperitoneum with ureteral obstruction. These complications are rare. The radiological features [including computed tomography (CT)] are described.


Effectiveness of pneumatic reduction of ileocolic intussusception in children.

A total of 158 consecutive therapeutic air enemas were performed upon 133 patients during a 2-year period. Perforation and/or an impairment of the general condition of the children were the only main contraindications for the reduction attempt (five patients). Successful reductions were achieved in 89% of cases with no complications. Operation was performed in all 17 cases of unsuccessful reduction: resection in four cases, easy manual reduction in nine, difficult manual reduction in two, and spontaneous reduction in two. There were 16 (12%) patients with one or more recurrent episodes. In 23 (16%) cases, following pneumatic reduction, a swollen ileocecal valve showing a multiple appearance was observed. This fact sometimes results in a differential diagnosis with incomplete reduction; in all these cases, small bowel aeration was always a sign of complete reduction. No significant difference was noted between a swollen ileocecal valve and patient age, duration of symptoms, presence of small bowel obstruction, and further recurrences. Air enema has improved our previous success obtained with hydrostatic reduction (79%), as well as being a simpler, cleaner, and faster technique for intussusception reduction in children.


Benign colorectal neoplasms undetected by colonoscopy.

This retrospective investigation assessed the sensitivity of colonoscopy for the detection of colonic polyps seen previously at barium enema examination. Included in the study were 77 patients with 106 polypoid lesions. Films showing lesions not subsequently seen at colonoscopy were reviewed and only those lesions with a visible point of attachment, exhibiting no movement in response to filling or change in position of the patient, and confidently diagnosed as a polyp by both reviewing radiologists were included among the 106 lesions. Sixteen lesions (15%) seen radiologically were not located colonoscopically, indicating an endoscopic sensitivity of 85%. Contrary to previous reports, most of the lesions missed endoscopically were in the left colon in regions thought to have been traversed by the instrument. The 15% false-negative rate found for colonoscopy is consistent with existing reports on colonoscopic errors and is approximately the same as the false-negative error rate for radiologic detection of colonic polyps.


Bile duct disease: prospective comparison of ERCP, CT, and fat suppression MRI.

The authors compared computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP), techniques commonly used to study the biliary tree, with pre- and post-Gd-DTPA breath-hold fast low angle shot (FLASH) and fat suppressed spin-echo in 28 consecutive patients with bile duct abnormalities detected on ERCP, including 11 patients with malignant disease and 17 patients with benign disease. ERCP, CT, and magnetic resonance (MR) images were prospectively interpreted in a blinded fashion and reviewed by consensus. ERCP characterized all cases of malignant disease by the presence of a narrowed bile duct lumen with irregular margins. CT and MRI detected all cases of malignant disease and characterized nine of 11 as malignant. In seven of these cases, CT and MRI showed thickening of extrahepatic bile duct walls greater than 5 mm. MRI images showed intrahepatic-enhancing periportal tissue in four cases, which was not seen on CT images, and which was biopsy-proven tumor extension. Benign disease was characterized on ERCP images by the demonstration of smooth tapered narrowings in 16 cases, whereas on CT and MR images it was characterized by mild to moderate dilatation of the intrahepatic bile ducts and wall thickness less than 5 mm in 13 cases. Overall ERCP correctly characterized 27 cases as benign or malignant and CT and MRI both characterized 25. The results of this study show a trend that ERCP is superior to CT and MRI for characterizing bile duct disease.


Extracapsular (satellite) hydatid cysts.

Sixteen percent of hydatid cysts in the liver in 185 patients examined by computed tomography (CT) showed daughter cysts located exterior to the fibrinous membrane of the main hydatid cysts. We call these extracapsular or satellite cysts. Extracapsular cysts have the same appearance as endogenous daughter cysts. Preoperative demonstration of these cysts is useful for planning an appropriate surgical treatment and reduction of the recurrence rate.


Significance of serum sialic acid in patients with Crohn's disease.

Serum sialic acid was measured to evaluate the activity of Crohn's disease. The sialic acid levels of patients with Crohn's disease in remission (CRP 0.0 mg/dl) were significantly higher than those of healthy subjects and postoperative patients with Crohn's disease. In patients in remission, serum sialic acid was significantly correlated with hemoglobin, hematocrit, platelet, and rapid turnover protein. Correlations with platelet, retinol-binding protein, and prealbumin were especially strong. From these findings, it was concluded that serum sialic acid level provides a useful index of the activity of Crohn's disease.


IgG subclass-containing cells around the lymph follicle in the human intestine.

The authors previously reported the ring-like distribution of IgG-containing cells around the lymph follicle in both the small and large intestine. In the present study, the distribution of IgG subclass-containing cells around the lymph follicle was examined in both the small and large intestine, including Peyer's patches, by the indirect immunoperoxidase staining method. A ring-like distribution of IgG subclass-containing cells was observed in 14 out of 21 lymph follicles including 4 Peyer's patches (66.7%) in the terminal ileum, and 4 out of 7 (57.1%) in the large intestine. The percentages of IgG1-, IgG2-, IgG3-, and IgG4- containing cells around the lymph follicle in the terminal ileum were 27.6 +/- 11.6%, 51.9 +/- 15.4%, 16.5 +/- 10.2%, and 4.0 +/- 3.1%, respectively, and those in the large intestine were 22.9 +/- 15.4%, 47.4 +/- 14.9%, 11.2 +/- 4.1%, and 18.5 +/- 7.7%, respectively. Thus, among the IgG subclasses, IgG2-containing cells showed the most frequent ring-like distribution around the lymph follicle. The IgG2 predominance around the lymph follicle in the intestine was markedly different from reported IgG1 predominance in the lamina propria in the large intestine. This difference in IgG subclass distribution may suggest different origins of the IgG subclass-containing cells in the lamina propria and in areas around the lymph follicle.


In situ characterization of mononuclear cell phenotype in intrahepatic lymphoid follicles in patients with chronic viral hepatitis.

The author examined liver biopsy specimens obtained from 596 patients with chronic viral hepatitis to clarify the role of lymphoid follicle formation in the portal spaces. Lymphoid follicles were observed more frequently in chronic hepatitis non-A non-B than in chronic hepatitis B and were also common in patients with anti-hepatitis C virus-positive non-A non-B hepatitis. Immunohistology revealed that these hepatic lymphoid follicles resembled the lymphoid follicles of synovial tissue in rheumatoid arthritis. In situ hepatitis B virus markers were examined in 40 patients with chronic hepatitis B showing lymphoid follicles. Among these, hepatitis B surface antigen (HBsAg) was detected in liver cells as well as in the center of the follicles in 19 patients (47.5%). By immune electron microscopy, the author confirmed the HBsAg-positive cells in the lymphoid follicles as follicular dendritic cells. These cells appeared to be a site for antigen trapping in the follicles, therefore, the intrahepatic lymphoid follicles are suggested to play a role in immune response to HBsAg in chronic hepatitis B.


Spontaneous bacterial peritonitis due to Clostridium perfringens in a patient with liver cirrhosis and pure red cell aplasia.

A 63-year-old man with decompensated liver cirrhosis and pure red cell aplasia complained of pyrexia, abdominal distention and abdominal pain. A diagnosis of spontaneous bacterial peritonitis (SBP), Conn's syndrome, was made upon the isolation of an anaerobe Clostridium perfringens from both ascitic fluid and peripheral blood. The bacteria were found to be susceptible to piperacillin, and administration of the antimicrobial agent markedly improved his SBP. The anaerobes should be kept in mind as one of the possible pathogens of SBP, although anaerobic infection has been reported to be quite rare in the disease.


Intrasplenic pancreatic pseudocyst: a case report.

An intrasplenic pseudocyst associated with the acute relapsing phase of chronic pancreatitis in a 51-year-old woman is reported, with a review of the Japanese literature. The patient was admitted with a complaint of left lateral and back pain. Abdominal US and CT revealed communicating cysts at the pancreatic tail and the subcapsule of the spleen. A repeat US and CT 1 month after admission demonstrated enlargement of the cyst at the pancreatic tail. ERCP revealed a dilated main pancreatic duct without any definite evidence of stenosis, and direct communication with the cyst at the pancreatic tail. Percutaneous cystography revealed that the subcapsular cyst of the spleen, the cyst of the pancreatic tail, and the main pancreatic duct communicated with each other. The cyst contained serous fluid with an amylase content of 57,500 IU/I. Distal pancreatectomy and splenectomy was performed. Histologically, there was a nonepithelial lining on the inner surface of the cysts at the pancreatic tail and the subcapsule of the spleen. Severe chronic inflammatory changes were present in the resected tail of the pancreas. Timely surgical treatment is advocated to reduce the mortality and morbidity associated with complications of intrasplenic pseudocysts.


Hepatitis E: review.

Hepatitis E is endemic, often provoking epidemics in many developing countries. It resembles hepatitis A clinically and epidemiologically but show a higher mortality rate and less infectiousness. Several lines of evidence strongly support the assumption that humans become immunized once they contract hepatitis E. Because of the low infectiousness, most of the adult population of endemic areas are susceptible to hepatitis E until an epidemic occurs, although they are almost always infected with hepatitis A during infancy. Epidemics are caused by accidental contamination by the hepatitis E virus (HEV) in feces of water provided to these people. The liver change reveals necroinflammation related to the immune-mediated mechanism. The HEV is molecularly cloned and sequenced and has a single-stranded, positive-sense RNA genome, 7,194 nucleotides followed by a poly (A) tail. There are three open reading frames. The non-structural gene, approximately 5 kb is located at the 5' end, while the structural gene, approximately 2 kb is located at the 3' end of the genome. There is a low level of nucleotide variations among HEV strains isolated from Myanmar and China and a single serotype appears to exist. The HEV may be a new RNA virus or belong to Caliciviridae family. Further investigation include in vitro propagation, elucidation of the gene replication, global seroepidemiology and vaccination of the HEV.


Shaking of the intact rat and intestinal angulation diminish the jejunal unstirred layer.

A sizeable pre-epithelial diffusion barrier (unstirred layer) is present during perfusion of the rat jejunum. In the present study, three rapidly transported compounds, CO, [14C]warfarin, and glucose (5.5 mmol/L), were used as probes to assess the ability of manipulations to reduce the unstirred layer. This layer was 700-800 microns thick in a 30-cm jejunal segment perfused in conventional fashion on the abdominal wall. Placement of four sharp angulations in the segment or replacement in the abdominal cavity reduced the maximal unstirred layer to 200-400 microns. Increasingly rapid shaking of the anesthetized, intact rat on a platform shaker produced progressively thinner unstirred layers. At 250 revolutions per minute, the maximal layer ranged from 32 to 68 microns for the three probes and may have been appreciably less if the epithelium offered appreciable resistance. Shaking yields a > 15-fold reduction in unstirred layer resistance and provides a means for measuring this resistance and for obtaining more accurate assessment of the true in vivo transport Michaelis constant (Km) of any compound.


Transforming growth factor alpha receptor binding sites in the canine gastrointestinal tract.

Transforming growth factor alpha (TGF-alpha) interacts with the same plasma membrane receptor as epidermal growth factor and is likely to play a role in proliferative and trophic processes of gastrointestinal tissues. The distribution of receptor binding sites for TGF-alpha was examined in the canine gastrointestinal tract (distal esophagus, stomach fundus, descending duodenum, jejunum, ileum, transverse colon) by tissue section autoradiography. 125I-TGF-alpha yielded a labeling pattern comparable to that of 125I-epidermal growth factor. Specific binding sites were particularly abundant in the mucosa in each region, with the highest concentration in the esophagus, colon, and stomach, as assessed by computer assisted densitometry. The density of binding sites was moderate in the stomach muscularis mucosae, low in the external muscle layer, and very low to undetectable in the submucosa throughout the gastrointestinal tract. In most cases, the greatest density within the individual regions was detected in the area characterized by the highest proliferative rate. Lymphoid aggregates were not labeled. In conclusion, TGF-alpha receptor binding sites are present throughout the gastrointestinal tract with differential patterns in the various regions; they are principally distributed to the mucosa and predominantly located to proliferative cell areas. These results are consistent with a role of this factor in regional regulation of proliferation and differentiation in the gut.


Importance of gastric acid in gastric ulcer formation in rabbits with antibody-induced prostaglandin deficiency.

The role of gastric acid in the development of gastroduodenal ulcers in prostaglandin-deficient conditions is unclear. In the current study, the effect of the proton pump inhibitor omeprazole on the formation of gastric ulcers was examined in a previously validated rabbit model of antibody-induced prostaglandin deficiency. Intragastric administration of 20 mg/kg omeprazole every 12 hours caused a profound suppression of gastric acidity (i.e., pH above 5 continuously). This same dose of omeprazole significantly reduced gastric ulcer formation induced by passive immunization with 6-keto-prostaglandin F1 alpha antibodies. It is concluded from these observations that gastric acid plays a critical role in the formation of gastric ulcers in rabbits with antibody-induced prostaglandin deficiency.


Surface hydrophobicity of gastric mucosa in Helicobacter pylori infection: effect of clearance and eradication.

Surface hydrophobicity of the gastric mucosa is reduced in peptic ulcer disease and Helicobacter pylori infection. This abnormality may be caused by H. pylori or may be an inherent defect. The aim of the present study was to clarify the relationship between H. pylori infection and mucosal hydrophobicity by examining the effect of eradication of the organism. H. pylori-positive patients with (n = 42) or without (n = 42) duodenal ulcer were randomized to receive ranitidine, bismuth, or bismuth plus antibiotics. Surface hydrophobicity of gastric mucosa was assessed by measurement of plateau-advancing contact angle. Measurements were performed at presentation, end of treatment, and 1 month later. Contact angle was unchanged after ranitidine (55 degrees vs. 56 degrees) but increased with bismuth (57 degrees-62 degrees; P < 0.05) and bismuth plus antibiotics (56 degrees-67 degrees; P < 0.0001). One month after treatment ended, contact angles in patients in whom H. pylori was not eradicated were not different from those before treatment (56 degrees vs. 56 degrees) but increased to a value similar to H. pylori-negative controls in patients in whom H. pylori was eradicated (56 degrees-69 degrees; P < 0.0001). It is concluded that reduced mucosal hydrophobicity in peptic ulcer disease is secondary to H. pylori infection and that this impaired mucosal defense provides a possible mechanism whereby H. pylori infection predisposes to acid/peptic digestion.


Adrenergic blockage does not restore the canine gastric migrating motor complex during vagal blockade.

Bilateral cervical cooling blockade of the vagi abolishes the gastric migrating motility complex (MMC), except for the pylorus. The present study investigated if this finding is caused by adrenergic inhibition of the stomach via sympathetic nerves entering the vagi below the level of the blockade. Stomach and upper small bowel motor activity was monitored in five chronic dogs whose vagosympathetic nerve trunks were previously isolated in bilateral, cervical skin loops to permit blockade by cooling. Adrenergic blockade was performed by an initial bolus injection of phentolamine (0.3 mg/kg) and propranolol (0.3 mg/kg) followed by a continuous intravenous infusion of the combined drugs at a rate of 1.5 mg.kg-1.h-1 for phentolamine and 0.3 mg.kg-1.h-1 for propranolol. Bilateral cervical vagal blockade abolished the gastric MMC, with persistence of phase III of the MMC in the upper small bowel. During combined vagal and adrenergic blockade, gastric contractions were absent in 4 of the 22 duodenal complexes observed. In the other duodenal complexes, intermittent gastric contractions were associated with all phases of the intestinal MMC, including phase I. At times, this contractile activity was accentuated during phase III but never reached the intensity of activity or showed the typical coordination features of the gastric MMC seen with the vagi intact. Therefore, unopposed adrenergic inhibition of the stomach does not explain the absence of the gastric MMC during vagal cooling blockade. Under normal circumstances, the vagus nerve is the most important pathway for central control of the appearance of the gastric MMC.


Currently used doses of omeprazole in Zollinger-Ellison syndrome are too high.

The efficacy of omeprazole increases during the first few days of administration, suggesting that long-term maintenance dose requirements in patients with Zollinger-Ellison syndrome may be lower than those initially established by upward titration. Long-term maintenance doses of omeprazole were prospectively reduced in 37 patients who had been taking omeprazole for 22 +/- 4 months. Successful reduction was defined as reduction to 20 mg once or twice daily with an absence of symptoms, endoscopy without evidence of active acid-peptic disease, and a gastric acid output of < 10 mEq/h. Sixty-eight percent of patients (25/37) were successfully reduced to 20 mg of omeprazole once (18/24) or twice daily (7/13). Ninety-five percent of patients (20/21) without multiple endocrine neoplasia type I, severe gastroesophageal reflux disease, or previous partial gastrectomy had safe reductions of doses. It is concluded that the currently used omeprazole maintenance doses in patients with Zollinger-Ellison syndrome are too high and advocated that the initial dose still be established by acute daily upward titration followed by gradual reduction once control of acid output has been achieved.