Randomised controlled trial of colostrum to improve intestinal function in patients with short bowel syndrome.

BACKGROUND/OBJECTIVES: Colostrum is rich in immunoregulatory, antimicrobial and trophic components supporting intestinal development and function in newborns. We assessed whether bovine colostrum could enhance intestinal adaptation and function in adult short bowel syndrome (SBS) patients. SUBJECTS/METHODS: Twelve SBS patients in this randomised cross-over study received 4 weeks oral supplement of bovine colostrum or an iso-energetic and iso-proteinaceous control (2.4 MJ/d, 500 ml/day) separated by a 4-week washout period. Patients were admitted four times for 72-h periods of fluid, electrolyte and nutrient balance studies. Meals, faeces and urine were weighed, and energy, macronutrient and electrolyte contents were analysed to calculate net nutrient uptake. Body composition was measured by dual-energy X-ray absorptiometry scans, and functional tests of handgrip strength and lung functions were performed. Eight patients completed the study and were included in the analysis. RESULTS: Both supplements (colostrum and control) not only increased protein (0.96 ± 0.42 MJ/d, P=0.004 1.03 ± 0.44 MJ/d, P=0.003) and energy (1.46 ± 1.02 MJ/d, P=0.005, 1.76 ± 1.46 MJ/d, P=0.01) absorption but also absolute faecal wet weight excretions (231 ± 248 g/d, P=0.002, 319 ± 299 g/d, P=0.03), compared with baseline measurements. Both supplements improved handgrip strength (P=0.03) while only the control supplement increased lean body mass (1.12 ± 1.33 kg, P<0.049). Colostrum was not found to be superior to the control. CONCLUSION: Intake of high-protein milk supplements increased net nutrient absorption for adult SBS patients, but at the expense of increased diarrhoea. Despite high contents of bioactive factors, colostrum did not significantly improve intestinal absorption, body composition or functional tests compared with the control.

Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer.

Until recently, fluorouracil (F) and leucovorin (L) had been considered the standard therapy for patients with colorectal cancer. However, several studies have shown that oral therapy with UFT/L or capecitabine is as effective as intravenous (i.v.) therapy and in addition it is claimed that patients prefer oral to i.v. therapy as long as efficacy is not compromised. In a previous crossover study by Borner et al., it was shown that 26 out of 31 patients preferred oral therapy with UFT/L to i.v. FL (Mayo regimen) [Borner M, Schöffski P, de Wit R, et al. Patient preferences and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002;38:349-58]. The objective of the present study was to investigate patient preference between i.v. FL and oral capecitabine using the design described by Borner. The Nordic FL schedule is a bolus regimen with efficacy comparable to other i.v. regimens and at the same time a very tolerable and easy administered regimen. We randomised 60 patients with colorectal cancer (53 patients received adjuvant therapy and seven patients received palliative therapy) to start therapy with either oral capecitabine or Nordic bolus FL. After 6 weeks of therapy (two courses of capecitabine or three courses of Nordic FL) patients were crossed over to the other regimen. After having completed 12 weeks of therapy the patients (49 evaluable patients) were asked to choose one of the regimens for a further 12 weeks of therapy. Patients had more side-effect when treated with capecitabine and a total of 30 out of 49 (61%) preferred the Nordic FL regimen and 19 (39%) preferred capecitabine. We conclude that patients prefer the regimen with less toxicity and that it is of minor importance whether the medication is administrated orally at home or i.v. at the hospital.

The feasibility of high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter: effect on thyroid function and size and pulmonary function.

Some patients with very large goiters (>150 mL) are not candidates for surgery. We evaluated the feasibility of high dose 131I in such patients. Twenty-three patients (2 men and 21 women; median age, 67 yr; range, 42-86 yr) with very large goiter (8 toxic) were treated with calculated high dose 131I [median, 2281 megabecquerels (61.6 mCi); range, 988-4620 megabecquerels (26.7-124.9 mCi)]. During the 12-month observation period, goiter reduction and tracheal anatomy were monitored by magnetic resonance imaging, and the respiratory capacity was monitored by pulmonary function tests. Five patients (22%) developed hypothyroidism. Thyroid volumes were at baseline, after 1 week, and after 1 yr [mean +/- SEM, 311 +/- 28, 314 +/- 26 (P = NS), and 215 +/- 26 (P < 0.01) mL]. The relative changes 1 week after therapy ranged from -14.1% to 15.3%. After 1 yr the mean size was reduced by 33.9% (range, 13.5-61.4%). Only the initial goiter size showed a significant negative correlation to the percent reduction. The smallest cross-sectional area of the trachea decreased 9.2% within 1 week after treatment, but eventually emerged with a 17.9% larger area [mean +/- SEM, 84.3 +/- 4.8, 75.5 +/- 5.1 (P < 0.01), and 98.2 +/- 6.0 (P < 0.01) mm2]. The inspiratory parameter, FIF50%, improved after an initial insignificant decline [baseline therapy, after 1 week, after 3 months, and after 1 yr (mean +/- SEM), 2.37 +/- 0.24, 2.20 +/- 0.21 (P = NS), 2.51 +/- 0.23 (P = NS), and 2.76 +/- 0.25 (P = 0.01) L/s]. FIF50% correlated significantly with the smallest cross-sectional tracheal area (baseline, 1 week, and 1 yr: r = 0.74; P < 0.001, r = 0.63; P < 0.005, and r = 0.46; P < 0.05). Changes in tracheal anatomy did not correlate with changes in either lung dynamics or goiter size. In conclusion, very large goiters can be reduced by a third, on the average, with high dose 131I therapy without any initial clinically significant tracheal compression. Tracheal cross-sectional area as well as pulmonary inspiratory capacity improve. No serious adverse effects are seen.

Hyperbaric oxygen treatment and pulmonary function.

Hyperbaric oxygen (HBO2) treatment exposes the lungs to the potentially toxic effect of free oxygen radicals and may lead to impairment of pulmonary function. HBO2 significantly improves wound healing in patients with osteoradionecrosis of the mandible following radiation therapy for intraoral cancer. In 18 consecutive patients with osteoradionecrosis of the mandible, pulmonary function was assessed during 6 wk of HBO2 treatment, applied daily in a monoplace chamber for 90 min and at a partial oxygen pressure of 2.4 atm abs. Pretreatment forced vital capacity (FVC) was 104 +/- 14% (mean +/- SD) of a reference population, the 1 s forced expiratory volume (FEV1) 95 +/- 20%, total lung capacity (TLC) 100 +/- 13%, and the carbon monoxide diffusing capacity (DL(CO)) 81 +/- 17% (P < 0.05, compared to reference population). These parameters remained unchanged throughout the treatment period (after 6 wk and expressed relative to the percentage of the expected value at baseline): deltaFVC: +4 +/- 8%; deltaFEV1: -2 +/- 4%; deltaTLC: +2 +/- 5%; deltaDL(CO): 0 +/- 9%; deltaRV 0 +/- 11%. It is concluded that intermittent HBO2 treatment in a monoplace chamber has no persistent effect on pulmonary function and can be offered even to patients with a reduced diffusing capacity.

The rat subcutaneous air sac model: a new and simple method for in vivo screening of antiangiogenesis.

An experimental rat model, the Subcutaneous Air Sac (SAS) model, was developed to provide an animal model in which neo-vascularization can be easily assessed in situ and quantified using a radiolabelled plasma marker. The SAS model was designed to replace a previous model where neovascularization was induced by chemical injury of rat or rabbit cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model the air sac replaces the cornea as a transparent avascular substratum in which vascularization can be observed. The air sac is induced by injection of air subcutaneously on the back of the animal. After 8 to 10 days a sufficient air sac has been established. The animal is anaesthesized and by a minor operation the cellulose sponge is implanted upon the air sac under the skin. The vasoproliferative effect of the cellulose sponge causes formation of new vessels which are macroscopically visible 10 days after implantation. The ability of the in vivo SAS model to show an antiangiogenic effect of a systemically applied test compound was investigated using the fumagillin analogue TNP-470 (ochloro-acetylcarbamoyl)-fumagillol) as a positive control at dose levels of 0, 1, 2.5, 5 and 10 mg/kg/day given subcutaneously for 10 days. The neo-angiogenesis was scored both in situ using a subjective point system and by measuring the 125I-activity of the implant and the membrane after an intravenous injection of 125I-labelled antibodies. The neo-angiogenesis was reduced by approximately 45-50% in animals treated with 5 or 10 mg/kg/day of TNP-470 compared to animals treated with the vehicle. The animals treated with 10 mg/kg/day TNP-470 showed signs of toxicity. The SAS model is considered highly relevant for in vivo testing of potential antiangiogenic drugs on humane grounds. The high reproducibility, the low cost and the technical simplicity of the method makes it attractive.

[A herbal preparation Resium in symptomatic gallstones. A preliminary study of the effect]. / Naturpraeparatet Resium ved symptomgivende galdesten. En proeliminoer undersøgelse af effekten.

Resium, an old Spanish herb, is claimed to remove gallstone symptoms and to dissolve gallstones. Ten patients admitted for cholecystectomy because of intermittent bile cholics participated in a study for six months to evaluate the effects. None had had complications to their gallstone disease, and all had normal liver biochemistry and a normal well-functioning gallbladder before entry into the study. By ultrasonography minor changes in both directions in stone number and volume were seen. Five patients experienced some relief of symptoms, while the rest had unchanged, or worse symptoms. No adverse events to Resium were seen. In conclusion no effect of Resium upon gallstone size and volume was seen. The design of the study does not allow any conclusion about symptomatic effect to be drawn.

Toxicity of vitamin D analogues in rats fed diets with standard or low calcium contents.

Sprague-Dawley rats were fed either a standard diet with 0.9/0.7% Ca/P or a semisynthetic low-calcium diet with 0.5/0.4% Ca/P and treated orally for 28 days with 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3], a synthetic analogue of the physiologically active form of vitamin D3, 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], at dose levels of 0.2 and 2.0 micrograms kg/day. The high dose caused severe hypercalcaemia with retarded growth, nephrosis, and structural bone changes in rats fed the standard diet. The same dose caused only slight hypercalcaemia without growth retardation or bone changes, and only minimally affected the kidneys in rats fed the low-calcium diet. Hypercalcaemia with less pronounced pathological changes was found in the standard diet low-dose rats, whereas no hypercalcemia or pathological changes were found in the low-calcium diet low-dose group. The rats fed the low-calcium diet tolerated 1 alpha(OH)D3 at dose levels up to 10 times higher than rats on the standard diet. The use of diets low in calcium and low in phosphorus will thus allow the administration of higher dosages of vitamin D compounds without causing hypercalcaemia. This may permit a better evaluation of the pharmacologic and toxic effects not directly associated with the calcium-regulating properties of vitamin D metabolites and analogues.

Oral and topical adrenergic beta-receptor blockers in glaucoma treatment. A multicenter study.

In a long-term multicenter open randomized study of 103 patients with glaucoma or intraocular hypertension, oral propranolol combined with 2% pilocarpine was compared with 0.5% topical timolol also combined with 2% pilocarpine, with respect to the effects on intraocular pressure and other signs of glaucoma. The results showed that the hypotensive effects were highly significant and equal for both treatments. There were no significant differences between the 2 groups in the amount of cupping of the nerve head or the visual field defects developing during treatment. An additive hypotensive effect was recorded when both propranolol and timolol were combined with pilocarpine, which indicates the development of tolerance to both beta-blockers. Pulse rate and blood pressure were moderately reduced in both groups, both significantly more so in the propranolol group. The investigation indicates that when combined with pilocarpine the 2 adrenergic beta-receptor blockers are equally effective. We believe that oral propranolol can improve drug compliance in the treatment of glaucoma.

The effect of N-6 and N-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure.

Diverging results from studies of marine oil supplementation to western diets initiated the undertaking of a double-blind crossover study, with administration to healthy volunteers for 4 weeks of either 10 g of fish oil or 10 g of vegetable oil. Each oil containing approx. 40% of n-3 and n-6 polyunsaturated fatty acids (PUFA) respectively. During the n-3 PUFA period, systolic blood pressure, plasma total lipids, triglycerides and VLDL concentrations fell significantly whereas plasma antithrombin-III (AT-III) rose. Cutaneous bleeding time increased significantly. In contrast only AT-III rose during the n-6 PUFA feeding, however, more marked than during the n-3 oil period. It is concluded that a n-3 PUFA oil supplement to the western diet exerts an effect that generally is considered as beneficial in terms of the risk of developing cardiovascular diseases. It is in this respect superior to that of n-6 PUFA, stressing the necessity of a more differentiated approach to advice on dietary PUFA enrichment than presently is exerted.

Glomerular filtration rate and extracellular fluid volume in insulin-dependent patients with diabetes mellitus.

To investigate whether the increased GFR in diabetic patients is related t an increased ECV, GFR ([51Cr] EDTA clearance) and ECV (distribution volume of [51Cr] EDTA) was determined in 26 insulin-dependent diabetic men aged 17 to 50 years (duration of disease 0.1 to 14 years) and compared to the results in normal men. Mean standard GFR +/- SD (that is, GFR corrected to a body surface area of 1.73 m2) was significantly higher in the diabetics than in 26 age-matched controls (127 +/- 21 ml/min vs. 107 +/- 15 ml/min, P less than 0.001). The same held true for the renal function assessed as the ratio GFR/ECV (0.58 +/- 0.10 hr-1 vs. 0.51 +/- 0.07, P less than 0.05). Regression analysis showed that the relation between ECV and body weight and between ECV and body surface area was the same in the diabetic patients as in 44 controls. The increased GFR but normal ECV indicates that the GFR alteration in diabetic patients reflects a real hyperfunction.

The glomerular filtration rate during penicillamine therapy in rheumatoid arthritis.

Twenty-one consecutive patients (14 women and 7 men aged 35-68 years, mean age 50 years) with chronic active RNA for 2-24 years (mean 12.7 years) had a normal glomerular filtration rate (GFR) (mean value 99.8 +/- 14.8% (S.D.) of sex- and age-dependent normal value) before penicillamine treatment. All patients had previously been undergoing gold treatment; no patient had signs of renal disorder, or diabetes. GFR (total 51Cr-EDTA plasma clearance) was measured before and after 3 and 6 months' penicillamine treatment, respectively. Treatment was stopped because of side effects in 4 patients, including one with renal side effects. In the remaining 17 patients there was a mean fall in GFR of 3.8 +/- 12.5 (S.D.) ml/min during 6 months' penicillamine treatment, which was not significant. There was no correlation between individual changes in GFR and penicillamine dose. The individual changes in GFR correlated well to individual changes in plasma creatinine. Repeated determinations of plasma creatinine should be done during penicillamine treatment.

Bone composition and parathyroid function in chronic renal failure.

The development of bone abnormalities has been studied in 24 patients with severe chronic renal failure. The glomerular filtration rate (GFR) was between 5 and 25 ml/min. The mean values of plasma calcium, degree of bone mineralization (P/Hypro) and bone mineral content (BMC) were subnormal, whereas the mean values of plasma phosphorus and serum parathyroid hormone (PTH) were elevated. Analysis of the data revealed that the various parameters became increasingly pathological with decreasing renal function. Serum PTH correlated inversely with both GFR and plasma calcium. The decrease in bone P/Hypro with decreasing renal function could be explained by an inverse correlation to serum PTH. Plasma alkaline phosphatase correlated inversely to both bone P/Hypro and BMC. The present study on individual patients with varying degrees of renal insufficiency shows that the development of secondary hyperparathyroidism correlates with a reduction in the degree of bone P/Hypro and suggests that significant bone changes appear when the GFR falls below 15 ml/min.

Controlled trial of 1apha-hydroxycholecalciferol in chronic renal failure.

24 patients with chronic renal failure (glomerular filtration-rate (G.F.R.) 5-25 ml/min) participated in a double-blind placebo-controlled trial of the effects of 1 alpha-hydroxycholecalciferol (1alpha-H.C.C.) 1 mug daily for eleven weeks. This treatment induced significant increases in the intestinal absorption of calcium and in plasma-calcium which reached normal levels within two weeks. It also induced a significant reduction of the raised serum levels of parathyroid hormone. No significant changes were induced in plasma-phosphorus, plasma-alkaline-phosphatase, or in the degree of bone mineralisation as measured by the phosphorus/hydroxyproline ratio in bone. The bone mineral content in the forearm measured by photon absorptiometry decreased to the same extent in the 1alpha-H.C.C. groups and in the placebo group. The fall in G.F.R. over eleven weeks was 2-5 times greater in the 1alpha-H.C.C. group than in the placebo group, but this difference was not significant. It is concluded that 1alpha-H.C.C. treatment in chronic renal failure does not affect the progressive loss of calcium from bone despite normalisation of plasma-calcium.