Budesonide versus prednisolone retention enemas in active distal ulcerative colitis

Methods: Efficacy and safety of the topically acting glucocorticosteroid budesonide retention enema (2.3 mg/ 11 5 mL) were compared with prednisolone disodium phosphate enema (31.25 mg/125 mL) in patients with active distal ulcerative colitis. The study was a randomized, multicentre trial, with two parallel groups and single-blind to the investigator. One hundred patients with active ulcerative colitis, not reaching beyond the splenic flexure as determined by endoscopy, were treated for up to 8 weeks. Results: Forty-five patients were randomized to receive budesonide and 5 5 to prednisolone. Both treatment groups improved significantly in terms of endoscopic and histological scoring during the study, but there were no statistically significant differences between the two groups. Clinical remission, defined as no more than three daily bowel movements without blood and endoscopically non-inflamed mucosa, was achieved in 16% of the patients in the budesonide group after four weeks and in 24% in the prednisolone group (N.S.). After 8 weeks treatment the clinical remission rate in the groups had increased to 36 % for budesonide and 47% for prednisolone (N.S.). Mean morning plasma cortisol levels were unchanged in the budesonide group, whereas they were significantly suppressed in the prednisolone group after 2, 4 and 8 weeks (P < 0.0001). Side effects were mild and rare in both groups. Conclusions: Treatment with budesonide enema in active distal ulcerative colitis was comparable, regarding efficacy, to treatment with conventional prednisolone enema. A prolongation of the treatment time from 4 to 8 weeks doubled the clinical remission rate in both groups. However, budesonide may be preferable to prednisolone since it causes less systemic effects as reflected by a lack of plasma cortisol suppression.     

Clinical experience with minimal flow xenon anesthesia

Xenon is a more potent anesthetic than nitrous oxide, and gives more profound analgesia. This investigation was performed to assess the potential of xenon for becoming an anesthetic inspite of its high manufacturing cost. Seven ASA I—-II patients undergoing cholecystectomy (n = 4), hernia repair (n = 2), or mammoplasty (n=l) were studied. Denitrogenation by 15–20 min of oxygen breathing under propofol anesthesia was followed by fentanyl–supplemented xenon anesthesia administered via an automatic minimal flow system which held the oxygen concentration at 30%. Xenon anesthesia lasted 76–228 min and 8–14 1 of xenon (ATPD) was used, of which 5.6–8.1 1 was expended during the first 15 min. Anesthesia appeared to be satisfactory, and the patients woke up rapidly after xenon was discontinued. The automatic system made minimal flow xenon anesthesia easy to administer, but nitrogen accumulation is still a problem. Assuming a xenon price of 10 US $ per litre, the average cost for xenon was about 65 US $ for the first 15 min and then about 25 USS for each subsequent hour of anesthesia.     

Skeletal Muscle Adaptations to Physical Training in Type II (Non-insulin-dependent) Diabetes Mellitus

Seven middle-aged men with manifest type II diabetes mellitus underwent an endurance training programme for 10–15 weeks. The maximal aerobic capacity, as well as the endurance capacity, was improved by 10% (p<0.05). The intramuscular glycogen store increased by more than 80% (p<0.05) from 350 μmol/g dw (dry weight), and the activities of citrate synthase and 3-hydroxy-acyl-CoA dehydrogenase increased by more than 50% (p<0.05) and 30% (p<0.05). The activity of glycogen synthase was decreased by approximately 20% (p<0.05), whereas lactate dehydrogenase remained unchanged. Capillaries/fibre and fibre area increased by more than 50% (p<0.05) and 30% (p<0.05) leaving the area of supply constant. Training did not influence fasting blood lipids and glucose, glycosylated hemoglobin, oral glucose tolerance, and insulin response to an oral glucose load measured 72 hours post-exercise. It is concluded that patients with manifest type II diabetes, as normoglycaemic individuals, adapt to physical training. However, no persistent effect on glucohomeostasis and lipaemia is produced by short-term training in the diabetic patients.     

Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats

Wilke , W. Lee & Person , A. E. G. 1992. Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats. Acta Physiol Scand 144 , 253–261. Received 26 June 1991, accepted 8 October 1991. ISSN 0001–6772. Department of Physiology, Colorado State University, Fort Collins, Colorado, USA and Department of Physiology and Biophysics, University of Lund, Sweden. Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg^-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 ± 2 mmHg vs. 38 ± 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 ± 0.03 vs. 0.31± 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 ± 2 to 44 ± 2 mmHg, P= 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 ± 0.02–0.42 ±0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post-surgery nephrectomized rats and their respective controls when combined (r = 0.89, P= 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r= 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups. We conclude that stop-flow pressure in remnant kidneys of pre-hypertensive rats is primarily determined by the post- to pre-glomerular resistance ratio, and increases in stop-flow pressure and post- to pre-glomerular resistance ratios in remnant kidneys are transient in the absence of systemic hypertension. The role of the renin-angiotensin system in determining the ratio and stop-flow pressure is dependent on time post-nephrectomy. Captopril-induced increases in stop-flow pressure and post- to pre-glomerular resistance ratio at 8 weeks, suggests that its primary effect at that time is not a preferential post-gIomerular vasodilation subsequent to reductions in intrarenal angiotensin II.     

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP)

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (P_sf) was increased from 18.5 to 25.7 nl min^-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP.     

Evaluation of an Educational Programme for Telephone Advisers in Primary Health Care

Marklund B, Silfverhielm B and Bengtsson C. Evaluation of aneducational programme for telephone advisers in primary healthcare. Family Practice 1989; 6: 263–267. Telephone advisers, usually registered nurses, have a very importantrole in the Swedish primary health care service. In order toimprove this service, a special educational programme has beenworked out for registered nurses working at a Swedish healthcentre. The purpose of this paper is to evaluate this educationalprogramme at one of the health centres. The quality of the telephoneadvice was evaluated by a blind observer. After the educationalprogramme the quality of advice was improved. Among the participatingnurses, the confidence and the satisfaction with the work increasedafter the educational programme.     

Renal nerve stimulation restores tubuloglomerular feedback after acute renal denervation

Renal nerves play an important role in the setting of the sensitivity of the tubuloglomerular feedback (TGF) mechanism. We recently reported a time-dependent resetting of TGF to a lower sensitivity 3–4 h after acute unilateral renal denervation (aDNX). This effect persisted after 1 week, but was then less pronounced. To determine whether normal TGF sensitivity could be restored in aDNX kidneys by low-frequency renal nerve stimulation (RNS), the following experiments were performed. Rats with aDNX were prepared for micropuncture. In one experimental group proximal tubular free flow (P_t) and stop flow pressures (P_sf) were measured during RNS at frequencies of 2, 4 and 6 Hz. In another series of experiments the TGF sensitivity was evaluated from the P_sf responses at different loop perfusion rates after 20 min of RNS at a frequency of 2 Hz. The maximal drop in P_sf (ΔP_sf) and the tubular flow rate at which half the maximal response in ΔP_sf was observed (turning point, TP), were recorded. At RNS frequencies of 2, 4 and 6 Hz, P_t decreased from the control level of 14.1 ± 0.8–13.1 ± 1.0, 12.4 ± 1.1 and 11.2 ± 0.8 mmHg (decrease 21%, P < 0.05), respectively, while at zero perfusion and during RNS at 2 and 4 Hz P_sf decreased from 42.5 ± 1.6 to 38.2 ± 1.4 and 32.8 ± 4.3 mmHg (decrease 23%, P < 0.05), respectively. The TGF characteristics were found to be reset from the normal sensitivity with TP of 19.0 ± 1.1 nL min^–1 and ΔP_sf of 8.7 ± 0.9 mmHg to TP of 28.3 ± 2.4 nL min^–1 (increase 49%, P < 0.05) and ΔP_sf of 5.8 ± 1.2 mmHg (decrease 33%) after aDNX. After 20 min of RNS at 2 Hz TP was normalized and ΔP_sf was 33% higher. Thus the present findings indicate that the resetting of the TGF sensitivity that occurred 2–3 h after aDNX could be partially restored by 20 min of RNS at a frequency of 2 Hz. These results imply that renal nerves have an important impact on the setting of the sensitivity of the TGF mechanism.     

The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions

The effect of the fatty acid cyclo-oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO₂) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg·kg^-1i. v.) reduced CBF to 50% of control without a measurable effect on CMRO₂. During hypercapnia (Pa_CO2 70–80 mmHg) the increase in CBF was reduced by about 80% but CMRO₂ remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg·kg^-1 and maximal effects were obtained with 3–5 mg·kg^-1. Following i. v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1–2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO₂ tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.     

Characterization of the prostanoid receptors and of the contractile effects of prostaglandin F2a in human pial arteries

The contractile and relaxant effects of various prostanoids were studied on isolated human pial arteries. Contractions were elicited with the following order of potency: U46619?U44069>PGB₂>PGF_2a>PGE₂?PGD₂>PGF_1a≥TXB₂, indicating that prostanoid-induced contractions probably are mediated by a thromboxane-sensitive receptor. Relaxation of PGF_2a-contracted arteries was induced with the order of potency: PGE₂> PGE₁>PGD₂?PGD₁. Vessels contrated by K⁺ were relaxed only by PGE,. Since PGI₂ was previously found to be more potent than all the prostanoids tested in the present study, relaxant responses are probably mediated via a PGI₂-sensitive receptor. The roles of free extracellular and cellularly bound calcium for the contractile effects of PGF_2a and K⁺ were estimated by incubating the arteries for various times in calcium-free medium containing 10^-5 M EGTA. Incubation for 5–10 min abolished K⁺-induced contractions, whereas after 40 min of incubation PGF_2a still induced contractions that reached 70% of control. The PGF_2a-induced contraction was biphasic in 8 out of 10 preparations. The second phase could be eliminated by increasing the EGTA-concentration to 10^-4 M, as well as by nifedipine pretreatment. In calcium-free, high K⁺ medium calcium-induced contractions were elicited at lower concentrations in the presence of PGF_2a. The results suggest that PGF_2a-induced contractions in human pial arteries are relatively independent of free extracellular calcium. PGF_2a may promote trans-membrane influx of calcium, as well as release calcium from seemingly superficially located cellular stores.     

Cytokine Gene Expression During Infeetion of Miee Lacking CD4 and/or CD8 with Trypanosoma cruzi

The expression of lymphokine genes during infection of virulent (Tulahuén) or mild ( CA-I ) strains of T. cruzi was studied in mice lacking CD4 and/or CD8 molecules. The increased susceptibility of CD4⁻ and CD4⁻ CD8⁻ mice to infection with CA-I or Tuiahuen was parallelled by diminished IFN-γ mRNA levels. Nitric oxide release and inducible nitric oxide synthase mRNA accumulation by cells from Tulahuen infected CD4⁻ mice was also diminished. CD8⁻ (but not CD4⁻ CD8⁻ mice) showed an increased IL-4 and IL-10 mRNA accumulation upon infection with both strains of T. cruzi. A T_h2-like' response (higher IL-4 and IL-10 mRNA to IFN-γ mRNA ratio), was also observed when cells from non-infected CD8 - mice were stimulated with T cell mitogens.