Lanfranchi Ga

TREATMENT OF ULCERATIVE COLITIS WITH HIGH-DOSE 5-AMINOSALICYLIC ACID ENEMAS

Abstract This study is a double-blind controlled trial in 86 patients of the efficacy of retention enemas containing 4 g 5-aminosalicylic acid (5-ASA), believed to be the active metabolite of sulphasalazine, compared with retention enemas of 100 mg of hydrocortisone for the topical treatment of mild or moderate ulcerative colitis. 5-ASA enemas given to 44 patients were significantly more effective than hydrocortisone enemas given to 42 patients, and produced 93, 93, and 77% remission in clinical, sigmoidoscopic, and histological terms, respectively, compared with corresponding remission rates of 57, 54, and 33% in the hydrocortisone treated patients.

A Laboratory Index for Predicting Relapse in Asymptomatic Patients With Crohn's Disease

Currently there are no completely reliable methods for predicting an impending relapse in Crohns disease. As approximately 50% of patients in remission [Crohns disease activity index (CDAI) less than 150] show some laboratory abnormalities, we inquired whether these alterations might be of value for predicting relapse. We prospectively studied 41 patients with Crohns disease who had been showing CDAI less than 150 for at least 6 mo before entering the study and who were not receiving any long-term treatment. The 41 patients were studied at the ninth and at the 18th month after inclusion in the study. Disease activity was monitored by CDAI calculation and by measurement of erythrocyte sedimentation rate, white blood cell count, hemoglobin, albumin, alpha 2-globulin, serum iron, C-reactive protein, alpha 1-glycoprotein, and alpha 2-antitrypsin. Seventeen of the 41 patients had a clinical relapse during follow-up. At the beginning of the study the patients who later relapsed showed a remarkable alteration of acid alpha 1-glycoprotein (p less than 0.0001), alpha 2-globulin (p less than 0.0003), and erythrocyte sedimentation rate (p less than 0.0006), in comparison with the patients who remained in remission. by discriminant analysis a prognostic index with these laboratory investigations provided a high percentage (88%) of accuracy according to the outcome at the 18th month.

A Double-Blind Clinical Trial to Compare the Effects of 4-Aminosalicylic Acid to 5-Aminosalicylic Acid in Topical Treatment of Ulcerative Colitis

5-Aminosalicylic acid (5-ASA) is the active component of Salazopyrin and induces a prompt and excellent improvement, when administered as high dosage enema, in patients suffering from active ulcerative colitis. However, the high instability of this metabolite makes its large use difficult. We aimed at finding a more stable preparation and therefore wondered whether another similar molecule, i.e. 4-aminosalicylic acid (4-ASA, generally known as p-aminosalicylic acid, PAS), which differs from 5-ASA only for the position of the amino group, might be a valid alternative. Therefore, 4-ASA at 2 g dosage, administered as rectal enema, was compared to an equivalent preparation of 5-ASA. We carried out a double-blind therapeutical trial, in which 63 patients, similarly matched for age, sex and extent of disease, took part. The analysis of the final results showed that in the 5-ASA group, 26 (81%) out of 32 patients improved clinically, 25 (78%) sigmoidoscopically and 15 (46%) histologically. In the group of the 31 patients treated with 4-ASA, 24 (77%) improved clinically, 24 (77%) sigmoidoscopically and 13 (41%) histologically. Since no difference was registered between the two types of treatment (p = 0.141, X2 test), 4-ASA could be a possible form of treatment for active ulcerative colitis.

Importance of laboratory parameters in the evaluation of Crohn's disease activity.

Some laboratory investigations are abnormal during the course of Crohns disease (CD). We investigated the trend of some of these laboratory tests in a group of patients with CD to study the relationships between an activity index made up of such laboratory parameters only (LCDAI) and the usual Crohns disease activity index (CDAI). One hundred thirty-one examinations of 63 patients were evaluated. At each investigation, besides calculation of the CDAI, 10 laboratory investigations were carried out. Three gastroenterologists independently gave an overall evaluation of the laboratory activity for each of the 131 examinations on the basis of the results of the blood tests alone. The sum of the evaluations was used as an independent variable on which a laboratory index was developed by multiple regression analysis. C reactive protein, red cell sedimentation rate, acid alpha 1-glycoprotein, alpha 1-antitrypsin, and white blood cells had an important share in the development of this laboratory index. The evaluation of the relationships existing between LCDAI and CDAI showed that in patients with moderate to severe clinical disease activity, LCDAI was constantly altered. The same happened in 55% of cases in clinical remission, which suggests an inflammatory activity that is not clinically evident. These results point to the advisability of supplementing a predominantly clinical index, such as CDAI, with a laboratory index such as LCDAI in the evaluation of CD.

Different patterns of intestinal transit time and anorectal motility in painful and painless chronic constipation.

Anorectal motility and gastrointestinal transit time were studied in 25 patients complaining of non-organic constipation. Colonic pain was reported by 14 patients, it was absent in the remaining 11. The group with painful constipation was composed of four men and 10 women and age onset of the symptom was 22.1 +/- 5.1 years. The other group was composed only of women and painless constipation was reported to have begun at 7.9 +/- 2.2 years previously. In the group presenting painful constipation higher values of the anal maximum resting pressure, of the amplitude of the rectoanal inhibitory reflex, lower values of sensation threshold, need to evacuate, maximum tolerable volume were recorded, in comparison with those registered in the painless constipation group. All these differences were significant. In the latter group the total transit time was always very slow (186.0 +/- 4.7 h), while it was quite variable in the other group, so that the mean was in the normal range (79.0 +/- 10.0 h). The data show that two different patterns of motor abnormalities can be recognised in constipated patients. The presence of colonic pain can suggest the characteristics of the underlying motor abnormality.

Topical administration of 5-aminosalicylic acid enemas in patients with ulcerative colitis. Studies on rectal absorption and excretion.

5-aminosalicylic acid (5-ASA) is a new treatment for patients suffering from ulcerative colitis but only limited information is available about its rectal absorption. We therefore studied seven patients with ulcerative colitis in remission, and five with active disease to determine acetylated and free 5-ASA plasma concentrations and urinary acetyl 5-ASA after the administration of three different types of enemas: (2 g 5-ASA/100 ml, 4 g/100 ml, and 200 ml). In patients in remission urinary acetyl 5-ASA excretion was dose and volume dependent (p less than 0.01; p less than 0.05) but this correlation was absent in active disease. Because aminosalicylates are usually eliminated through the kidney, these low values (10% in active disease and 19% in those in remission) suggest that the beneficial action may be local. Urinary recovery was significantly lower in patients with active disease (p less than 0.01; p less than 0.02). No accumulation of 5-ASA was found in plasma after repeated daily administration.

Retrograde spread of 5-aminosalicylic acid enemas in patients with active ulcerative colitis.

In an attempt to know the exact retrograde spread of high-dosage 5-aminosalicylic acid enemas, we have studied eight patients with active left-sided colitis, by adding a small amount of barium sulfate to the enemas and by checking the spread radiologically after 15 minutes, 1 hour, and 6 hours. Four grams of 5-aminosalicylic acid in 100-ml enemas and 4 gm in 200-ml enemas were used. The same experiment was repeated in a subsequent attack, with enemas labeled with technetium-99m and checked by scintiscans in five of these patients. We always have observed a volume-dependent spread of enemas but, interestingly, in the patients studied with technetium-99m there was always a wider spread than that which was detected with barium enemas. In all five patients, 100-ml enemas reached the splenic flexure. In two patients with total colitis, a progression of 100-ml technetium-99m enemas was performed in the transverse colon, but the maximum opacity remained in the left side. We can conclude that 4 gm of 5-aminosalicylic acid in 100-ml enemas can be suitable for treating patients with left-sided colitis, and will represent a valid addition for patients with more extensive colitis.

Motor effect of dopamine on human sigmoid colon. Evidence for specific receptors.

The effect of dopamine on human sigmoid motility has been studied in 26 subjects. To record mechanical activity of the sigmoid colon, two small, air-filled balloons mounted on a probe introduced through a sigmoidoscope were used. The recordings were made at a distance of 25 and 15 cm from the anal edge. Dopamine was infused for 10 min after a 30-min control infusion of physiologic solution. Mean amplitude, mean duration, mean frequency, percentage of motor activity, and motility index of the pressure waves were determined. The motor response to dopamine was characterized by an increased baseline pressure with phasic waves superimposed. Dopamine produced a significant response at the dose of 5 μg/kg/min. Alpha and beta antagonizing agents failed to oppose the effect of dopamine, while anticholinergic drugs enhanced its motor action. These studies suggest that dopamine may stimulate the motor function of human large bowel through specific receptors.

The possible utility of steroids in the prevention of relapses of Crohn's disease in remission. A preliminary study.

In Crohns disease, prednisone is believed to be ineffective for relapse prevention. Because all patients with Crohns Disease Activity Index lower than 150 and with some altered lab tests (erythrocyte sedimentation rate, C-reactive protein, alpha-1-acid glycoprotein, alpha-1-acid antitrypsin, and white blood cell count) had a clinical relapse in 18 months of follow-up, we tried to ascertain whether methylprednisolone could reduce the risk of clinical relapse in such patients. Eighteen patients were included in a controlled study against placebo. Nine patients were treated with methylprednisolone at a dosage of 0.25 mg/kg daily for a period of 6 months; treatment was discontinued if disease relapsed or if lab tests were normalized. During the steroid treatment, 1 of 9 patients showed a clinical relapse; in 7, the normalization of lab tests was obtained; in 5 of these 7 patients a relapse occurred within 1 month after the suspension of the treatment; in 1 patient, lab tests remained altered. In those 9 patients on placebo, relapses occurred in 7. We conclude that methylprednisolone was effective in the prevention of relapses for patients in clinical remission but with altered lab tests.

Dopamine-induced migrating myoelectrical complex-like activity in human duodenum

The effect of dopamine on human gastric and small intestinal interdigestive motility was investigated in 12 subjects. Intestinal motility was recorded by means of a four-lumen polyvinyl probe with four open tips located 15 cm apart, continuously perfused with distilled water. In each subject during the same study, after recording two consecutive spontaneous phase III of migrating myoelectrical complexes and when a phase II appeared, dopamine was infused intravenously twice in a dose of 5 μg/kg/min for 15 min with an interval of 20 min between each infusion. In six subjects, the second dopamine infusion was preceded by a treatment with sulpiride (10 mg, intravenously, as bolus) or domperidone (10 mg, intravenously, as bolus), each considered a highly selective dopamine antagonist. The results show that dopamine stimulates duodenal motility producing a pattern similar to that observed in phase III of spontaneously occurring migrating myoelectrical complexes. The second dopamine infusion reproduced in all cases the same pattern of motility as observed during the first infusion. Sulpiride and domperidone prevented the effect of dopamine in all cases. It is therefore suggested that dopamine-induced duodenal motility may involve specific dopaminergic receptors.