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Objective The aim of this study was to assess the effect of infliximab on quality of life in patients with active Crohn's disease (CD) inadequately responsive to concomitant therapies. Methods We examined responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) from patients enrolled in a previously reported, randomized, placebo-controlled study. Patients with active CD received a single intravenous infusion of either placebo or infliximab 5, 10, or 20 mg/kg. Most patients received stable doses of mesalamine, corticosteroids, azathioprine, or 6-mercaptopurine throughout the study. Changes from baseline in overall IBDQ score and individual dimensions at 4 weeks postinfusion were compared. Results Patients treated with infliximab had a significantly larger improvement in overall IBDQ score than those treated with placebo at 4 weeks (p < 0.001). Infliximab-treated patients also had larger improvements in all IBDQ dimensions: bowel (p = 0.007), social (p = 0.002), emotional (p < 0.001), and systemic (p < 0.001). A significantly larger proportion of infliximab-treated patients reported having normal or near-normal frequency of bowel movements in the past week (p < 0.001), full or a lot of energy (p = 0.019), and no or hardly any difficulty doing leisure or sports activities (p = 0.011), and being extremely or very satisfied with their personal life (p = 0.046). They also significantly differed in responses regarding fatigue, frustration, ability to work, general well-being, depression, anxiety, and anger resulting from bowel problems. Conclusions These results indicate that infliximab significantly improved quality of life in patients with active CD, increasing their ability to work and participate in leisure activities, and decreasing feelings of fatigue, depression, and anger.

The aim of the study is to investigate which of two treatment options of saline lavage induced ARDS in rabbits is better in terms of oxygenation and prevention of barotrauma: combined high peak pressure ventilation with surfactant administration and inhaled nitric oxide or veno-venous ECMO combined with low peak inspiratory pressure ventilation.After saline lavage (10 cc/kg repeated as long as foamy retrieval was observed) two combined therapeutic strategies were examined: ventilation with high inspiratory pressures (35 cm H2O) with additional exogenous surfactant administration (100 mg/kg) and inhaled nitric oxide (10 PPM) (n=5, group 1) and low inspiratory pressure (20 cm H2O) ventilation under veno-venous ECMO support (n=5, group 2). The FiO2 was maintained at 1.0 in both groups. The paO2/FiO2 ratio was calculated in 30 minute intervals for 4 hours. After that the animals were sacrificed and the lungs examined macro- and microscopically. Aeration was described in a semiquantitative method using the alveolar expansion index. Oxygenation in group 1 was significantly better than in group 2, it increased significantly after surfactant but not after additional nitric oxide administration. However, the lungs in group 1 showed severe signs of baro/ergotrauma (Hyaline membranes, air leaks, infiltration of polymorphonuclear (PMN) granulocytes and macrophages, break down of alveolar capillary membranes) after 4 hrs of combined therapy, whereas the lungs in group 2 appeared normal. Adding surfactant and NO to a high tidal volume ventilation improved oxygenation, but did not prevent baro/ergotrauma. Ventilation with low inspiratory pressures combined with ECMO caused little baro/ergotrauma but adequate oxygenation could not be achieved, probably due to anatomical features of the rabbit which do not allow appropriate blood flow within the ECMO-circuit.

Rats were trained with two running protocols previously demonstrated to result in enhanced cardiac performance. Control groups included free-eating sedentary animals and food-restricted animals in which the body weights were the same as the runners. Calcium binding by isolated sarcoplasmic reticulum (SR) was slightly but significantly increased in SR from runners at low but not high calcium concentrations at 15 s and 1 min. Calcium uptake in the presence of 1 mM oxalate was increased in SR from runners. Actomyosin ATPase activity was increased by 10% (P less than 0.001) with one running protocol but not with the other. Myosin Ca2+ ATPase activity and actin-activated ATPase activity were also slightly increased in hearts of runners. In food-restricted cardiac actomyosin ATPase was significantly decreased. Actomyosin ATPase activity was found to be normal in hearts of sedentary animals subjected to water immersion without exercise. Therefore, physical training of rats by running, which produces a cardiac mechanical advantage similar to training by swimming, is not accompanied by cardiac biochemical changes of the same magnitude as in the hearts of swimmers.

To evaluate the combined effects of cardiac overload imposed by hypertension and chronic swim training on coronary vascularity, female rats were made hypertensive by unilateral renal artery stenoses and were exercised in an 8- to 10-wk swimming program. Maximal coronary flow was assessed in isolated retrograde buffer-perfused hearts under conditions of minimal coronary resistance (15 microM adenosine or anoxia). Sedentary normotensive animals, sedentary hypertensive animals, and normotensive animals exposed to a swimming program were also studied. Swimming was associated with an 18% increase in heart weight and with increases in both absolute (ml/min) and relative (ml X g-1 X min-1) maximal coronary flow. Hypertension was associated with a 32% increase in heart weight but with a decrease in absolute and relative coronary flow compared with controls. The combined stimuli resulted in a 63% myocardial hypertrophy and a 19% increase in absolute flow. Relative coronary flow (g tissue-1) was similar in hearts from hypertensive sedentary animals and hypertensive swimmers. These data indicate that the coronary vascular deficit that accompanies the cardiac hypertrophy of hypertension is not worsened by the superimposition of an exercise load that exaggerates the hypertrophy.

The purpose of this study was to determine whether a chronic swimming program could reverse the decreased cardiac function and altered myosin biochemistry found in hearts of rats with established renal hypertension. Ten wk after the onset of hypertension [midpoint (m)], hearts from normotensive controls (C) and hypertensives (H) were studied in an isolated working heart apparatus, and myosin biochemistry was analyzed. Half of the control and hypertensive animals were then subjected to a 10-wk swimming program (Sw) and their hearts were compared with those from age-matched sedentary rats. Body weight was no different at the midpoint of the study between Cm and Hm or at the end point (e) of the study among Ce, Swe, He, or H-Swe. Swimming had no effect on blood pressure in either normotensive or hypertensive rats. Dry heart weight was increased by 46% in Hm compared with Cm and by 36% in He, 21% in Swe, and 61% in H-Swe when compared with Ce. Hypertension was associated in both the mid- and end-point studies, with decreases in coronary flow, stroke work (both per gram left ventricle), ejection fraction, and midwall fractional shortening. In addition, actin-activated myosin adenosinetriphosphatase (ATPase) activity was decreased in Hm and He associated with an increase in the content of the V3 myosin isoenzyme. Although the coronary deficit was not corrected in H-Swe, stroke work, ejection fraction, and fractional midwall shortening were normalized compared with control hearts. Myosin ATPase activity and the myosin isoenzyme distribution were similarly restored in H-Swe.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological cardiac hypertrophy was produced in female rats by subjecting them to a swimming program for 8 wk. Conditioned rats (C) had body weights similar to sedentary control rats (S), but hearts from C weighed 33% more than hearts from S. Heart function was assessed in an isolated working-heart apparatus at similar heart rates and aortic diastolic pressures and over a range of 5-20 cmH2O left atrial filling pressure (LAP). At any given LAP, absolute values for cardiac output and coronary flow were greater (p less than 0.001) in C than S, but when these values were normalized for dry left ventricular (LV) weight, no differences were observed. Peak LV systolic pressure and ejection fraction were greater (p less than 0.01) in C than S at all LAP. Derived measures of contractility calculated at the midwall demonstrated greater (p less than 0.01) velocity and extent of circumferential fiber shortening in C compared with S. Therefore, chronic swimming in female rats leads to enhanced contractile performance of the left ventricle despite a marked degree of hypertrophy. These results contrast with our earlier observations in female rats trained by running where neither hypertrophy nor enhanced function were observed.

To determine the effects of graded insulin therapy on cardiac function and biochemistry, rats were made diabetic by streptozotocin (50 mg/kg) and subsequently treated with either 3 U of insulin per day (D3) or 5 U/day (D5) and compared with untreated diabetic rats (D phi) and a nondiabetic control group (C). Blood glucose, water consumption, and heart and body weights in D3 and D5 showed dose-dependent responses between those of D phi and C. Cardiac function was studied at similar heart rates and similar left atrial and aortic pressures in an isolated working heart apparatus. Hearts from D phi showed significant decreases in end-diastolic pressure, peak left ventricular systolic pressure, and positive dP/dt, whereas these values in D3 and D5 were similar to those in C. The isovolumic relaxation period was significantly longer in the D phi group, intermediate between D phi and C in D3, and the same in D5 and C. Ca2+-ATPase activity of myosin and actin-activated Mg2+-ATPase activity was depressed in D phi, partially corrected in D3, and completely corrected in D5. Myosin isoenzyme distribution displayed a shift from the predominant V1 pattern observed in C to a predominant V3 pattern in D phi. Treatment with 3 U of insulin per day partially corrected the isoenzyme abnormality, and treatment with 5 U/day restored the isoenzyme distribution to normal. These results indicate that gross cardiac contractile function can be normalized with insulin dosages that are not sufficient to correct hyperglycemia, polydipsia, or body and heart weight.(ABSTRACT TRUNCATED AT 250 WORDS)

To study effects of physiologic hypertrophy on contractile protein ATPases and sarcoplasmic reticulum, hypertrophy was caused in female Wistar rats by a chronic swimming program. Nonhypertrophied hearts of female control sedentary rats and rats made to run on a treadmill program were also examined. The swimming program, but not the running program, resulted in a significant increase in heart weight. Actomyosin ATPase activity was also increased by 15% in the hearts of swimmers but not runners. Similar increases were observed for Ca2+-activated myosin ATPase activity and actin-activated ATPase of myosin. Sarcoplasmic reticulum from the hearts of swimmers showed increased calcium binding and calcium uptake as a function of time and of calcium concentration. Sarcoplasmic reticulum ATPase activities were not altered by hypertrophy. These findings in physiologic hypertrophy contrast with those of pathologic hypertrophy in which ATPase activity of contractile proteins and calcium binding and uptake of sarcoplasmic reticulum have generally been found to be depressed.

To evaluate the effects of sex hormones on heart function and biochemistry, gonadectomy (GX) was performed in postpubertal male (M) and female (F) rats and compared with sham-operated controls (SH). The groups were MSH; MGX; MGX replaced with testosterone 3 mg/day s.c. (MGX + T), FSH, and FGX replaced with estrogen 2 mg/day (FGX + E), progesterone 0.4 mg/day (FGX + P), estrogen and progesterone (FGX + EP), or testosterone 2 mg/day (FGX + T). Body weight was decreased in MGX and was decreased further in MGX + T. Heart weight was decreased in both MGX and MGX + T. Body weights were increased in FGX and FTX + P and were increased further in FGX + T but were normal in FGX + E and FGX + EP. Heart weights were unchanged in F groups except in FGX + T, where it was increased. Cardiac performance in perfused hearts, as measured by stroke work, ejection fraction, fractional shortening and mean velocity of circumferential fiber shortening, was decreased in MGX but was slightly increased in MGX + T. Papillary muscle studies showed increases in time to peak tension and one-half relaxation in MGX, but these were decreased in MGX + T. Isotonic shortening studies showed decreased velocity of shortening in MGX and increased velocity in MGX + T. Heart function was significantly decreased in FGX and FGX + P compared with FSH but was similar to FSH in FGX + E and FGX + EP. FGX + T had greater stroke work and ejection fraction than FSH and FGX.(ABSTRACT TRUNCATED AT 250 WORDS)