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A study of a new osmotic purgative for colonoscopy. Is Golytely worth its salt?

An osmotic laxative containing polyethylene glycol and sodium sulfate (Golytely Braintree Laboratories, Inc., Braintree, MA) is widely used to clean the colon for colonoscopy. However, its salty taste makes the mixture unpalatable. We therefore tested the claim that a similar solution but without sodium sulfate (Golytely-RSS Braintree Laboratories, Inc., Braintree, MA) makes preparation of the colon more acceptable to patients in a double-blinded randomized controlled trial. Colonic preparation using polyethylene glycol with or without sodium sulfate was randomized in 100 patients due to undergo colonoscopy. The overall acceptability of the regimen was measured on a linear analogue scale and an estimate of symptoms was obtained. Body weight and serum electrolytes, urea, creatinine, hemoglobin and hematocrit were determined before and after preparation in order to assess fluid absorption. The efficacy of colonic cleansing was graded by the colonoscopist. Four patients did not complete the protocol, 47 received the regimen containing sodium sulfate and 49 received the regimen without it. The two groups did not differ in age or body mass. There was no statistical difference in the overall acceptability of the two regimens to the patients (median acceptability rating 74 for regimen with sodium sulfate, range 4-100 compared with 77 for regimen without, range 3-100, p = 0.32, Mann-Whitney test). Nor was there any difference in taste, nausea, vomiting, cramping or perianal discomfort or in the endoscopists' rating of the cleanliness of the colon. The serum sodium concentration rose slightly (mean 1.6 mmol/L) when the regimen with sodium sulfate was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Cathartics↗

Increase in magnesium plasma level after orally administered trimagnesium dicitrate.

Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.

Administration, Oral↗

The effect of preliminary bowel preparation on a simple test of colonic transit in constipated subjects.

The abdominal distribution of orally ingested radioopaque markers is used to assess total and segmental colonic transit in constipated patients, but interpretation may depend on whether studies are carried out on a full colon or one cleared of faeces. We asked 25 severely constipated patients (age 18-74; 22 F, 3 M) to ingest 50 polyethylene markers (4 mm x 2 mm) at breakfast on 2 occasions 1 month apart. No bowel preparation was used for study 1 but for the second study 2 doses of Sodium Picosulphate (2 x 10 mg) were taken 3 days before ingestion of the markers. All subjects reported a good result which had ceased a day before taking the markers. Marker distribution was assessed by a plain abdominal film taken 72 hours after ingestion. All 25 subjects had more than 50% of markers present at 72 h in study one. Of these 4 showed evidence of outlet obstruction with more than 50% of ingested markers in the rectum. In the remaining 21 subjects markers were distributed throughout the colon in a pattern indicating colonic inertia. Following the administration of purgative there was no significant change in the mean number of markers retained but patterns of marker distribution for individual subjects did alter. Of the 21 patients who previously had colonic inertia, 3 showed outlet obstruction and 1 showed no evidence of delayed transit. Of the 4 patients with a pattern of outlet obstruction in the first study, 2 showed no evidence of delayed transit after Picolax.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Histomorphology of the liver by damage with phenolisatine-containing laxatives (Recurrent chronic cholangiohepatitis)].

In the case of 36 female patients who were anamnestically known to have taken laxatives, semiquantitative histological investigations with laparoscopically obtained liver needle biopsies were effected after the exposition with preparations containing phenolisatine. The time gap until exposition was 12 to 24 h (16 cases), 48 h (8 cases), 72 to 96 h (4 cases) and 7 to 14 days (4 cases). The histological result after the exposition is an acute cholangiolitis of the allergic-hyperergic type with edema and a dense eosinophile infiltration of the portal fields with destruction of the epithelium of preformed bile ducts and portally proliferated ductles. In addition, the parenchyma of the liver shows a pleomorphism of the cells in form and colour with a cellular edema and with disseminated acidophilic necroses and necrobioses of the individual cells as well as with little reactive proliferation of the Kupffer's cell. After a period of 8 days the acute process has more or less subsided. Also, in the majority of cases there are histological signs of an aggressive chronic hepatitis of type IIa, partially in the active stage with piece-meal necroses and partially stabilized or in the process of healing. A transition to the picture of hepatitic cirrhosis is possible. In serious cases the picture of a chronic non-purulent destructive cholangitis can be simulated by the hepatocellular and canalicular damage. Thirty-one bioptic pre-examinations from the same results, whereby the acute cholangiolitical exacerbation can be attributed to an exposition of the patients themselves. The clinical picture of the phenolisatine damage in its entirety is induced by medication and is described as a recurrent chronic cholangiohepatitis. Similarities exist between the liver damages caused by chlorpromazine and arsphenamine. When medication is discontinued, the morphologic substrate recedes leaving behind an inactive fibrosis or cirrhosis. The formal and known causal pathogenetic connections are discussed with regard to this clinically important liver disease. Guidelines are then given for histological diagnosis of this damage caused by medication. 14% of the female patients with a histological picture of aggressive chronic hepatitis and hepatitic cirrhosis are affected by this type of liver damage.

Adult↗

Effect of diphenolic laxatives on Na+-K+-activated ATPase and cyclic nucleotide content of rat colon mucosa in vivo.

1. The effect of bisacodyl and oxyphenisation on the Na+-K+- and Mg2+-activated ATPase and on the mucosa levels of cAMP and cGMP was investigated in transporting ligated loops of the rat colon in acute studies and in chronic feeding experiments 2. The specific activity of the Na+-K+-ATPase was lowered in both types of experiments, concomitantly with a reduction in net sodium absorption. The specific activity of the Mg2+-activated ATPase was unaffected. 3. The cAMP content per mg protein was elevated and the cGMP content decreased in the acute experiments in which the effect on transport was most marked. The content of cyclic nucleotides returned to normal within 2 h whereas absorption, Na+-K+-ATPase specific activity and the mucosal potential difference were still significantly depressed at that time. In chronic experiments with bisacodyl, cAMP was not affected and cGMP was increased in colon loops exhibiting reduced absorption. 4. The results indicate that the inhibition of the Na+-K+-activated ATPase by diphenolic laxatives may play a role in the inhibition of intestinal fluid absorption caused by these compounds. The increase of cAMP in acute experiments could point to a cAMP-mediated stimulation of secretory processes under this condition.

Animals↗

Appearance of 14C-polyethylene glycol 4000 in intestinal venous blood: influence of osmolarity and laxatives, effect on net water flux determination.

In anaesthetized rats the appearance rate of 14C-polyethylene glycol 4000 (14C-PEG 4000) was measured in the intestinal venous blood after intraluminal administration into a jejunal, ileal, and colonic segment. The absorption rate was small, especially in the colon (0.5-4.2% within 60 min in an intestinal segment of about 300 mg wet tissue weight depending on the batch of 14C-PEG 4000). The absorbed PEG in the plasma consisted mainly of molecules with lower molecular weight than 4000 which were included in the commercial batches of 14C-PEG 4000. The appearance rate of 14C-PEG decreased with time after single dose but remained constant, when a 14C-PEG solution was perfused continuously through the intestinal lumen. A hypotonic solution increased and a hypertonic one decreased slightly the absorption of PEG in the jejunum and ileum but not in the colon. The influence of bisacodyl (100 mgl(-1)) and ricinoleate (10 mmol l(-1)) on the absorption of PEG was small or absent, while deoxycholate (5 mmol 1(-1)) raised the absorption rate considerably, predominantly of the high molecular weight fraction. If in intestinal absorption studies a batch of commercial 14C-PEG 4000 with a small low molecular weight fraction is used, the error in the determination of net water flux caused by the absorption of PEG can be neglected. The influence of osmolarity and laxatives is insignificant. Bile acids increase the intestinal permeability of PEG 4000, so that the net water flux determination can be biased considerably.

Absorption↗

Colon motility and colo-anal reflexes in chronic idiopathic constipation. Effects of a novel enterokinetic agent cisapride.

Motor activity of the colon and reflex behaviour of the anal sphincters in normal subjects and in patients with idiopathic constipation were studied using a novel probe with 5 open-end tips to measure pressures, and 3 balloons for stimulation of the distal colon. Constipation appeared to be associated with an increased threshold of the inhibitory relaxation reflex of the internal anal sphincter (41.7 in normals and 65.7 in patients), and in particular with a blunted sensation of the defaecation urge (51.0 in normals and 112.8 in patients). Single-blind comparison with a placebo showed that cisapride, a new gastrointestinal prokinetic substance, had a significant effect on the sensation threshold, which normalized or improved in 15 out of the 16 patients studied.

Adult↗

In vitro tolerability of human nasal mucosa: histopathological and scanning electron-microscopic evaluation of nasal forms containing Sandostatin.

An in vitro human nasal model was developed as a tool to study the local tolerability of nasal powder forms using excised nasal mucosa in a diffusion chamber. The suitability of this model was tested using Sandostatin (SMS) an octapeptide analog of somatostatin, as a reference drug enhanced by Avicel (microcrystalline cellulose) or lactose (100 mesh). The standard nasal spray vehicle was taken as a harmless control and 1% chenodeoxycholate (CDC) as a harmful control in terms of local tolerability. The extent of peptide permeation was determined by measuring SMS concentration in the receiving chamber. The labeling of SMS was detected by immunoperoxidase staining on cross sections. The local tolerability for all tested forms was assessed by histopathological examination and scanning electron microscopy. The apparent permeation coefficient allowed us to rank the absorption of the tested drug forms as Avicel > spray = lactose > 1%CDC. For all formulations, SMS was detected in the epithelium. No changes of the nasal mucosa could be observed with Avicel, lactose or nasal spray vehicle in the presence or absence of SMS. 1%CDC with or without drug showed an immediate destruction of the nasal epithelium. The validation of this in vitro model using human nasal mucosa will be further discussed as a tool for assessing the local tolerability of intranasally applied test substances.

Absorption↗

Prolongation of life span in hypertensive rats by dietary interventions. Effects of garlic and linseed oil.

The effects of long-term dietary application of garlic (dried powder, 0.5% in weight of standard chow; G group) or linseed oil (2.5%; L group) as well as a combination of both interventions (L + G group) on the life span of hypertensive rats (SHR SP) was investigated. A further group fed with standard chow served as control (C). The dietary interventions were started at the age of three weeks. Besides regular measurements of the systolic arterial blood pressure (oscillometrically at the tail artery) as well as of heart rate and body weight, autopsy and histological investigations were performed. Both diets, and particularly their combination, prolonged life span significantly (mean values (days) C: 434.5 +/- 23.5; G: 453.2 +/- 16.2; L: 470.0 +/- 26.2; L + G: 494.8 +/- 39.2). There was no significant interaction of the factors garlic and linseed oil. Systolic blood pressure as measured during the compensatory stage (data used until the 39th week of life) was significantly lowered by both garlic (mean -5.8 mm Hg), linseed oil (mean -6.3 mm Hg), and their combination (mean -11.3 mm Hg). The animals died as a consequence of congestive left and right ventricular failure with ventricular hypertrophy, dilatation, myocardial fibrosis and cellular infiltration, left ventricular atrial thrombosis (in most cases), and terminal pneumonia. On the other hand, arteriosclerotic plaques and signs of cerebral stroke could not be detected. Except for the degree of hypertrophy, which was lower in the treated groups, no differences were obvious regarding the morphological findings at the time of death. There was a significant positive correlation between mean blood pressure and the degree of left ventricular hypertrophy. Furthermore, a significant negative correlation between mean blood pressure and ventricular hypertrophy on the one hand and survival on the other hand was obvious provided the total number of animals was considered, however, not within the individual groups. The same applies to the relation between the reduction of left ventricular hypertrophy and life span. The relatively slight hypotensive effect of both dietary interventions as well as the results of previous investigations speaks in favor of a substantial influence of factors independent of blood pressure. In view of controversial results and interpretations in international literature, the mechanisms involved need further study.

Animals↗

Reliability of chemical tests for fecal occult blood in hospitalized patients.

In 39 hospitalized patients with suspected gastrointestinal bleeding and given intravenous 51Cr-labeled red cells, reactions of three chemical spot tests for fecal occult blood were compared with the "true" blood loss as determined by stool radioassay. Guaiac reagent and orthotolidine (Hematest) tablets were extremely sensitive, but yielded false-positive reaction rates of 72% and 76%, respectively on the 240 stool specimens compared. A modified guaiac test (Hemoccult) exhibited a false positive rate of 12%. Of the 27 patients entering the study due to positive guaiac or Hematest screening tests, 17 (63%) were not bleeding. Hemoccult, approximately 1/4 as sensitive as guaiac and Hematest, could miss lesions with low rates of bleeding unless multiple stools were tested. While barium had no effect, iron therapy or laxatives tended to lower both false-positive and false-negative reactions for all reagents. A positive Hemoccult test usually indicated significant gastrointestinal bleeding and would appear to be the test of choice provided at least 3 stools are tested to minimize false-negative results.

Barium Sulfate↗