Influência da acemetacina e indometacina sobre a eliminaçäo gastrintestinal de sangue em pessoas sadias e em reumáticos / Influence of acemetacin and indometacin on gastrointestinal blood loss in normal volunteers and rheumatic patients

Em um ensaio clínico realizado em 12 voluntários sadios determinou-se a perda total de sangue gastrintestinal através de eritrócitos marcados pelo Cr51. O ensaio duplo-cego cruzado revelou uma diferença altamente significativa (p < 0,001) entre a indometacina e acemetacina após administraçäo oral durante sete dias de ácido 1-(p-clorobenzoil) - 5-metoxi- 2-metilindol- 3-acetoxi-acético (acemetacina, TV 1322, Mostanol) 200mg/dia, indometacina 200mg/dia e placebo. A perda total média de sangue, em um período de sete dias, foi de 12,4ml com indometacina, 4,5ml com acemetacina e 5,0ml com placebo. Em um ensaio clínico com 16 pacientes reumáticos em uso prolongado de medicamentos antiinflamatórios näo-hormonais encontrados habitualmente no mercado, determinou-se de igual modo a perda total gastrintestinal de sangue. Em um ensaio duplo-cego cruzado com período de wash-out foram comparadas as quantidades de sangue eliminadas durante um tratamento de sete dias com acemetacina (240mg/d) com as quantidades eliminadas durante o mesmo período com indometacina (200mg/d). Também chamou atençäo uma diferença altamente significativa (p < 0,001) entre os dois preparados. Com indometacina a eliminaçäo total de sangue por semana foi de 13,8ml, com acemetacina 6,5ml. Durante o período de wash-out foram eliminados em média 6,0ml de sangue por semana. Näo houve diferença entre os resultados de ambos os ensaios. As investigaçöes realizadas em 23 pacientes e 12 voluntários näo revelaram nenhum indício de que a nova droga antiinflamatória acemetacina provoque lesöes da mucosa do trato gastrintestinal evidenciadas por perda de sangue

[Effect of 3-(4-chlorphenyl-) 1-phenyl-1H-pyrazole-4-acetic acid (lonazolac-Ca), diclofenac-Na and indomethacin on the gastrointestinal blood loss]. / Uber den Einfluss von 3-(4-Chlorphenyl-) 1-phenyl-1H-pyrazol-4-Essigsäure (Lonazolac-Ca), Diclofenac-Na und Indometacin auf die gastrointestinale Blutausscheidung.

According to a Latin Square-2 block study design gastrointestinal blood loss after medication with lonacolac-Ca (200 mg t.i.d.), diclofenac-Na (50 mg t.i.d.) and indomethacin (50 mg t.i.d.) was investigated in 6 healthy volunteers. Blood loss was estimated by measuring 51Cr-labelled erythrocytes in the faeces. Each active substance was taken for one week in randomized order, followed by a 7-day period of placebo administration (wash-out period). Stool samples were collected daily, also during placebo periods. Average weekly blood loss was 13.76 ml after lonacolac-Ca, 12.57 ml after diclofenac-Na and 23.687 ml after indomethacin. Blood loss was significantly lower with lonazolac-Ca and diclofenac-Na than with indomethacin (p less than 0.001). There is no difference statistically between the two former substances.

[The influence of acemetacin and indometacin on gastrointestinal blood loss in normal volunteers and rheumatic patients (author's transl)]. / Uber den Einfluss von Acemetacin und Indometacin auf die gastrointestinale Blutausscheidung bei Gesunden und Rheumatikern.

In a clinical trial on 12 healthy volunteers total gastrointestinal blood loss was measured with 51Cr-labelled erythrocytes. This double-blind cross-over study showed a highly significant difference (p < 0.001) between indometacin and [1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-acetoxy[acetic acid (acemetacin, TV 1322, Rantudil¿) after oral application of 200 mg acemetacin, 200 mg indometacin per day and placebo for a week. Average total blood loss within seven days was 12.4 ml after indometacin, 4.5 ml after acemetacin and 5.0 ml after placebo. In a clinical trial on 16 rheumatic patients taking commercial non-steroidal antiinflammatory drugs over a long time total gastrointestinal blood loss was determined likewise. After a preceding wash-out period the blood loss due to acemetacin (240 mg daily) and indometacin (200 mg daily) for seven days was compared. There was a highly significant difference (p < 0.001) between both drugs. Total weekly blood loss was measured as 13.8 ml due to the treatment with indometacin and 6.5 ml due to acemetacin. During the wash-out period blood loss was detected as 6.0 ml weekly. There was no difference between the results of both trials. These clinical trials on 35 patients and volunteers do not give any indication that the new antiinflammatory drug acemetacin may cause mucosal lesions in the gastrointestinal tract evedenced by blood loss.

[Effect of furosemide on the hemodynamics of the kidney medulla during salt depletion]. / Die Wirkung von Furosemid auf die Hämodynamik des Nierenmarks bei Salzverarmung.

UNLABELLED: In sodium depleted rats cortical and medullary blood flow was studied before and after 4-chloro-N-(2-furylmethyl)-5-sulfamoyl-anthranilic acid (furosemide). 86Rb was used as an indicator of renal hemodynamics. Its activity was assessed in systemic blood and in tissue slices of the kidney. At the beginning of the experiments the animals were loaded p.o. with 1.3 ml/100 g b.w. of isotonic saline. 3 h later a rapid i.v. injection of 50 muCi (=5.6 MBq) 86Rb was given to 12 control and 9 furosemide treated animals. RESULTS: After 0.7 mg/100 g b.w. of furosemide the sodium and water excretion rises to 820% and 860% resp. (p less than 0.0005). Systemic body hematocrit increases from 47 to 49%. The renal cortical blood flow is not influenced by furosemide. Compared with controls there is a decrease in blood flow through the outer medulla from 1.57 +/- 0.65 to 1.00 +/- 0.37 ml/g.min, through the inner medulla from 0.75 +/- 0.30 to 0.59 +/- 0.23 ml/g.min, and through the papillary tips from 0.85 +/- 0.40 to 0.46 +/- 0.18 ml/g.min. However, these hemodynamics changes are not significant. It is concluded that the decrease in renal medullary hemodynamics of furosemide-treated rats is due to a stimulation of the renin-angiotensin system.

[14CO2 exhalation tests. Diagnostic improvement in gastroenterologic diseases]. / 14CO2-Exhalationstests. Bereicherung gastroenterologischer Diagnostik

For evaluation of 14CO2-breath-tests the three most employed tests, namely glycero-14C-tripalmitate-test, 14C-lactose-tolerance-test, and 14C-glycin-cholate-test, were performed in healthy volunteers (n = 69), patients with chronic pancreatitis (n = 18), manifest malassimilation (n = 8), lactase deficiency (n = 15), and patients, in whom a disturbed enterohepatic bile salt circulation was suspected (n = 19). Usefulness of malabsorption tests was limited by many false normal results. Cholylglycin-breath-test on the other hand was sensitive, but clinical significance remained questionable. In our opinion simple performance and lacking discomfort are no sufficient arguments for 14CO2-breath-test.

[Differentiation of the effect of diuretic urine extracts on the renal medullary blood flow (author's transl)]. / Differenzierung der Wirkung von diuretischen Harnextrakten auf die Nierenmarkdurchblutung

In sodium depleted rats urine extracts of hydrated healthy human volunteer cause an increase in water excretion of 52% (p less than 0.005) and in sodium excretion of 45% (p less than 0.005). Cardiac output of the volumen loaded rats increases from 465 +/- 104 ml to 528 +/- 128 ml/kg-min (p=n.s.). Rb86 is used as an indicator for renal hemodynamics. Compared with controls there is an increase in blood flow through the outer medulla from 1.57 +/- 0.65 to 2.28 +/- 0.61 ml/g-min, through the inner medulla from 0.75 +/- 0.30 to 1.01 +/- 0.30 ml/g-min, and through the papillary tips from 0.85 +/- 0.04 ml to 1.21 +/- 0.25 ml/g-min. The experiments show that the diuretic/natriuretic urine extracts influence the hemodynamics of the renal medulla.However, since the significance level of the enhanced medullary blood flow is only low (p less than 0.1) it is impossible to find out the direct site of action of the urine extracts.

[The effect of Voltaren on the gastrointestinal excretion of blood (author's transl)]. / Uber den Einfluss von Voltaren auf die gastrointestinale Blutausscheidung

24 subjects were treated with Voltaren 150 mg per day for 21 days, or with Naproxen 750 mg per day and ASA 3.0 g per day. In all patients the physiological excretion of blood from the intestine markedly increased, to a very great extent with Naproxen and ASA. From this aspect, Voltaren is highly significantly superior in maximal doses to the other two medicaments.

[Hypotonic examination of esophagus in pediatric radiology (author's transl)]. / Die Anwendung der hypotonen Osophagusuntersuchung in der pädiatrischen Radiologie

Report on 22 children whose esophagus was radiologically examined under maximum hypotonia, using i.v. Buscopan in a dose of 1 mg/kg body weight (highest 50 mg). The main indication are varices of the esophagus which can be shown much better than with conventional techniques. But also small axial hiatus herniae and esophageal stenoses are better shown.

[New procedure in the diagnosis of maldigestion. Studies with 3-H palmitic acid and 14-C tripalmitate in normal subjects and patients with chronic pancreatitis]. / Uber ein neues Verfahren in der Diagnostik der Maldigestion. Untersuchungen mit 3H-Palmitinsäure/14C-Tripalmitat bei Normalpersonen und Patienten mit chronischer Pankreatitis

3H-palmitic acid and 14C-tripalmitate dissolved in 1.0 g indian corn oil/kg body weight were administered to 29 patients with chronic pancreatitis and 25 control subjects. For the following 8 h 3H and 14C radioactivity in serum lipids and 14CO2 in expired air were measured at 2-hour intervals. Triglyceride absorption was significantly lowered in the pancreatitis group, while the wide dispersion in healthy subjects precluded reliable information on 14C-triglyceride absorption alone in individual cases. When related to palmitic acid absorption, however, reduced triglyceride absorption was much more evident and could be clearly demonstrated in 21 of the 29 patients with chronic pancreatitis. Since none of them had severe pancreatic insufficiency, the new double isotope method presented here appears to offer a very sensitive means of detecting maldigestion or slowed triglyceride hydrolysis. Compared with the 3H-fatty acid absorption, a relatively reduced triglyceride absorption was found in many cases without steatorrhea or otherwise demonstrable pancreatic insufficiency. Additional measurement of 14CO2 appears to be worthless, since in our patients specific activity of 14CO2 in the expired air was not reduced even in cases with mild steatorrhea.