Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial.

BACKGROUND: Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. METHODS: This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. RESULTS: Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. CONCLUSION: Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).

Ingestion of toxic Microcystis aeruginosa by dairy cattle and the implications for microcystin contamination of milk.

Microcystin (MCYST) toxins can be produced by the bloom-forming cyanobacterium Microcystis aeruginosa. They are chemically stable compounds and have both acute and chronic effects on the health of mammals, including cattle and humans. Cattle will drink water containing lethal cell concentrations of M. aeruginosa. When cattle consume sub-lethal doses of microcystins, the fate of those toxins is unknown. We provided drinking water containing 1 x 10(5) cells ml(-1) M. aeruginosa (strain MASH01-A19) to four lactating Holstein-Friesian dairy cattle for 21 days to determine if MCYST-LR produced by the cyanobacteria, could be detected in milk produced by the cattle. Cattle consumed up to 15 mg MCYST-LR at an ingestion rate of 1.21 microg kg (live weight) d(-1). Analysis by HPLC and ELISA indicated that no detectable amounts of microcystin from the cyanobacteria were present in the milk obtained from the treated animals. Based on the level of quantitation of the ELISA analyses, the maximum possible concentration in the milk was less than 2 ng l(-1). This is more than three orders of magnitude less that the concentration that could be considered problematic for milk of 0.86 microg l(-1) which we calculated using the World Health Organization derived tolerable daily intake for MCYST-LR and the per capita daily consumption of milk in Australia.

Action of long(R3)-insulin-like growth factor-1 on protein metabolism in beef heifers.

Insulin-like growth factor-1 (IGF-1) is perhaps the most important endogenous factor controlling growth. Most studies to date in livestock have shown that IGF-1 has greatest efficacy when animals are in a catabolic state. We have determined the effects of an i.v. infusion of the IGF-1 analog Long(R3)-IGF-1 on protein metabolism in beef heifers that were slowly losing liveweight because of restricted feeding. There was a tendency for both whole-body protein and skeletal muscle protein to be conserved in Long(R3)-IGF-1-treated heifers. Long(R3)-IGF-1 administration markedly reduced the plasma concentrations of all amino acids measured and glucose. There was a significant change in the profile differences of endogenous plasma IGF-1 concentrations during the 8-hr infusion period, with plasma IGF-1 decreasing sharply in the test group. There was a significant difference in mean profiles for plasma IGF-2 between the test and control groups. Overall, plasma IGF-2 for the control group decreased only slightly over time (about 40 ng/ml), whereas the test group decreased dramatically (by about 140 ng/ml). Increased plasma concentrations of a 31-32-kDa IGF-binding protein (possibly IGF-binding protein-1) in the treated group was detected by radioligand blot. We found that Long(R3)-IGF-1 infusion tended to preserve whole-body and muscle protein in beef heifers on a low-quality diet, and suggest that further investigation of this treatment may provide an alternative approach to reducing weight loss during the dry season.

Growth, nitrogen metabolism, and cardiac responses to clenbuterol and ketoclenbuterol in rats and underfed cattle.

Two beta-adrenoceptor agonists, clenbuterol and ketoclenbuterol, were examined for their effects on growth and cardiac tissue. In female rats, clenbuterol caused a 48% increase in weight gain (P < .05), with improved feed efficiency (26%; P < .1) and increased muscle mass (9%; P < .1). Ketoclenbuterol had less effect on weight gain (30%) and feed efficiency (16%) and did not increase muscle mass. Next we studied the adverse cardiovascular effects of these compounds. Neither drug increased the force of contraction of isolated rat ventricular papillary muscle. Clenbuterol was potent at causing an increase in the rate of contraction of isolated rat atria, and when fed to cattle over 2 d, the drug caused heart rate to increase by 92 to 117%. In contrast, ketoclenbuterol was not a potent stimulator of atrial rate in the rat, and in cattle it caused a smaller increase in heart rate than clenbuterol (12 to 27%). Finally, cattle that were underfed to simulate dry-season tropical pasture conditions were treated with clenbuterol or ketoclenbuterol for 35 d. Ketoclenbuterol caused no beneficial changes in N metabolism. The results obtained with clenbuterol were equivocal, and might have been confounded partly by the refusal of some treated animals to eat all the feed offered. Although clenbuterol did not cause a reduction in total urinary N output relative to control animals, marked reductions in plasma urea concentrations and in urea synthesis were observed (23 to 53%; P < .001). We conclude that ketoclenbuterol is not effective for attenuation of dry-season protein loss in cattle. Clenbuterol seems to be less effective in underfed cattle than in well-fed cattle, and further evidence is required to judge whether compounds of this nature are likely to benefit tropical cattle under harsh grazing conditions.

Effect of growth path on the tenderness of the semitendinosus muscle of Brahman-cross steers.

The growth paths of 36, nine-month-old Brahman-cross steers were modified to determine the effect of their growth history on tenderness of the semitendinosus (ST) muscle. Steers were assigned to one of three treatment groups. One group of steers (uninterrupted group) was grazed on improved tropical pasture for 257 days and had an average weight gain of 0.6 kg day(-1). The other two groups were fed a restricted diet of low-quality grass hay and lost on average ~ 13% of their initial live weight over 100 days. These groups were then regrown for 157 days on either pasture (pasture finished) with the uninterrupted group, or on a grain-based feedlot diet (grain finished). Growth rates of the previously restricted groups during the regrowth phase were indicative of compensatory growth and were significantly different (p < 0.05) at 0.76 (sem 0.03) kg day(-1) and 1.22 (0.05) kg day(-1), pasture and grain finished groups, respectively. Growth rates for both restricted groups were significantly different (p < 0.05) from the uninterrupted group [0.55 (0.02) kg day(-1)]. At slaughter, the grain finished group had heavier carcases, higher dressing percentages and more fat coverage, than either the uninterrupted or pasture finished groups, the latter being significantly lighter than the uninterrupted group. Tenderness was assessed by shear, compression (C) and adhesion (ADH) measurements. Shear peak force (PF) values of cooked ST samples did not differ significantly between groups. However, PF values of pressure-heat treated ST samples from the grain finished group were significantly less (p < 0.05) than comparable values from the uninterrupted group suggesting a reduced contribution of connective tissue to toughness. The pasture finished group mean PF value was not significantly different from either the uninterrupted group or grain finished group means. C and ADH values were significantly less (p < 0.05) in the grain finished group compared to the pasture finished groups values, again indicating a reduced connective tissue contribution to toughness. We conclude that the physical properties of the connective tissue component of the ST muscle may be altered by rapid compensatory growth after a weight loss phase and reduce the connective tissue contribution to toughness which may enhance meat tenderness.

Bovine myofiber characteristics are influenced by postweaning nutrition.

This study determined the extent to which bovine longissimus lumborum muscle (LLM) myofibers are influenced by nutrition for 120 d from weaning and the time-course of recovery after severe postweaning nutritional restriction. After weaning, 3 groups of Belmont Red cattle, a tropically adapted breed, were fed to achieve rapid growth (RG, > or =0.6 kg of BW gain/d; n = 16), slow growth (SG, 0.2 kg of BW gain/d; n = 17), or BW loss (WL, 10% loss of weaning weight; n = 17) over 120 d. They were then grazed as 1 group at pasture with forage supplementation for 600 d until slaughter at approximately 500 kg of BW. Samples of LLM were taken from 8 to 12 animals per treatment 6 d before (baseline) and 115, 204, 324, and 476 d after commencement of the study and from all cattle at slaughter (d 721). Myofiber characteristics were determined by immunocytochemical staining of myosin heavy chains. Cross-sectional areas (CSA) of the major myofiber types 1, 2A, and 2X in WL were reduced at d 115 compared with baseline and with the growth groups (all P < 0.001); however, there was little difference in the percentage of the different myofiber types (all P > 0.10). Differences in CSA of the major myofiber types between WL and the growth groups at 115 d were smallest for type 1 (slow oxidative) and greatest for type 2X (fast glycolytic). Consequently, the relative area (percentage of total myofiber area) of type 1 myofibers in WL was significantly greater at 115 d than in the growth groups (P < 0.001). During recovery from postweaning nutritional restriction, significant differences in major myofiber type percentages were not evident (all P > 0.10), and by 721 d CSA of myofiber types differed little between the treatment groups, although SG had greater CSA of type 1 (P < 0.05) and type 2A (P < 0.01) myofibers than WL and RG. At 721 d, the relative area of type 2A myofibers was less in WL compared with SG (P < 0.01) and RG (P < 0.05) and of type 2X myofibers greater (P < 0.05) in WL compared with SG. It is concluded that in the LLM of cattle undergoing severe nutritional restriction immediately postweaning, the size of the more glycolytic fiber types is more adversely affected than the more oxidative types, resulting in an increased relative area of type 1, slow oxidative myofibers. However, given adequate time and nutriment at pasture, LLM myofiber characteristics of cattle recovered to near normal after severe, chronic nutritional restriction immediately postweaning, consistent with earlier findings for beef quality.

The effect of the alpha 2-adrenergic agonist, guanfacin, on the energy metabolism of steers fed on low-quality-roughage diets.

The effect of the alpha 2-adrenergic agonist, guanfacin, on the energy metabolism, feed intake and live weight (LW) change of steers was studied in three experiments. In the first, the metabolic rate of twelve steers was measured after a 72 h fast. The next day, after a 96 h fast, six steers were injected intramuscularly with 15 mg guanfacin in sterile saline (9 g sodium chloride/l) and six with sterile saline alone, and metabolic rate was measured again. Treatment significantly (P less than 0.01) lowered metabolic rate by approximately 20% (53.9 v. 66.8 kJ/kg per d). In the second experiment twelve steers were fed on long-chopped, low-quality roughage (Pangola grass (Digitaria decumbens) hay) ad lib. for 6 weeks. Six steers were continuously infused through a jugular catheter with 15 mg guanfacin/d (about 40 micrograms/kg LW) in sterile saline. The other six served as controls. There was no significant effect of treatment on feed intake (g dry matter (DM)/kg LW) or the rate of LW loss. Treatment significantly (P less than 0.05) increased the retention time of fluid (17.9 v. 22.1 h) in the alimentary tract. In the final experiment twenty-three steers were divided into four treatment groups and fed on long-chopped, low-quality roughage (Pangola hay). Treated animals were continuously infused with guanfacin at the rate of 20, 40 or 80 micrograms/kg LW per d. Control steers were not infused. At the end of the 6-week feeding period metabolic rate was measured after a 72 h fast. Regardless of dose, guanfacin significantly (P less than 0.01) lowered metabolic rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Utilization of low-quality roughage by Bos taurus and Bos indicus cattle. 1. Rumen digestion.

Six Hereford and six Brahman steers were fed ad lib. Pangola grass (Digitaria decumbens) and Spear grass (Heteropogon contortus) hay alone and supplemented with rumen-degradable nitrogen and sulphur and minerals. The rumen digestion of the two feeds was determined by reference to the disappearance of substrate from nylon bags suspended in the rumen and withdrawn after intervals ranging from 8 to 120 h. The digestion of the unsupplemented Pangola grass diet occurred more rapidly in Brahmans than in Herefords and was associated with higher rumen ammonia concentrations in Brahmans (40 v. 16 mg/l). The rumen NH3 concentrations were increased to over 100 mg/l by supplementation. The digestion rate increased in both breeds after supplementation and the breed difference disappeared. Increases in digestion rate were not achieved above NH3 concentrations of 60-80 mg/l. Spear grass, especially the cell-wall-constituent fraction, was more resistant to digestion than Pangola grass. Digestion of the unsupplemented Spear grass diet proceeded more rapidly in Brahmans than in Herefords. The digestion rate in Brahmans were similar irrespective of whether the diet was supplemented or not. Supplementation increased digestion rate in Herefords.

Utilization of low-quality roughage by Bos taurus and Bos indicus cattle. 2. The effect of rumen-degradable nitrogen and sulphur on voluntary food intake and rumen characteristics.

In a number of experiments voluntary food intake of three low-quality roughages, either alone or supplemented with rumen-degradable nitrogen and sulphur and minerals, was measured in Brahman (Bos indicus) and Hereford (Bos taurus) steers. The chaffed hays were Spear grass (Heteropogon contortus) (6.2 g N/kg organic matter (OM)), Pangola grass (Digitaria decumbens) (7.9 g N/kg OM), and Pangola grass (12.0 g N/kg OM). Rumen characteristics relating to rate of fluid outflow from the rumen were also determined. There was no significant difference between breeds in the dry-matter intakes of the unsupplemented diets which ranged from 11.3 to 17.8 g/kg body-weight (BW) by Herefords and from 11.8 to 16.1 g/kg BW by Brahmans. Supplementation of Spear grass with N and S significantly (P less than 0.05) increased intake by Herefords (24%) but not by Brahmans. When the lower-N Pangola grass was supplemented there was a significant increase in intake by both breeds with the magnitude of the response in Herefords (42%) (P less than 0.001) being greater than that in Brahmans (15%) (P less than 0.05). The intakes of both the supplemented Spear grass and the lower-N Pangola diets were significantly (P less than 0.05) greater by Herefords than Brahmans. There was no breed difference in intake when the higher-N Pangola grass was supplemented. Both breeds recorded an 8% intake response to supplementation, although the increase was only significant (P less than 0.05) in Herefords. The mean retention time of fluid in the rumen on the unsupplemented Pangola grass diet of lower N content was 12.7 h in Brahmans compared with 17.5 h in Herefords (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of energy requirements of steers fed on low-quality-roughage diets using trenbolone acetate.

1. Six steers implanted with 300 mg trenbolone acetate and six steers not implanted were fed on low protein, low-quality-roughage diets ad lib. in two experiments. The steers were Hereford (Bos taurus) x Brahman (Bos indicus) crossbreds (50:50), initially of about 400 kg mean live weight (LW). In the first experiment of 8 weeks duration roughage was given alone. In the second experiment of 6 weeks duration the diet was supplemented with 100 g urea and 4.6 g sulphur daily. The same steers were implanted in each experiment. At the conclusion of each experiment metabolic rate was measured after a 72 h fast. 2. In the first experiment control and implanted steers had similar rates of LW loss (0.57 and 0.59 kg/d respectively). Implanted steers had significantly (P less than 0.01) lower feed intakes (12.8 v. 10.9 g dry matter (DM)/kg LW), significantly (P less than 0.01) lower fasting metabolic rates even after adjustment for intake (83.3 v. 74.5 kJ/kg per d) and significantly (P less than 0.01) lower plasma insulin concentrations (24 v. 19 mu units/ml). Differences in plasma concentrations of free 3,5,3'-triiodothyronine (T3), non-esterified fatty acids and urea-nitrogen were not significant. 3. In the second experiment intake of the supplemented diet was similar in both control and trenbolone acetate-treated steers (19.5 and 20.0 g DM/kg LW respectively). LW gains were 0.23 and 0.41 kg/d for control and implanted steers respectively, the difference being significant (P less than 0.05). Fasting metabolic rate (76.9 v. 70.7 kJ/kg per d) was significantly (P less than 0.05) lower in implanted steers.

The injured spleen: should consideration be given to conservative management?

This report is a retrospective study over a 13 year period of 267 patients who underwent splenectomy. The incidence of associated major abdominal injuries following blunt trauma in these patients was 8%. Over half of these associated injuries were diagnosed pre-operatively. Sixty-nine per cent of the patients were haemodynamically stable before operation. Patients who suffered splenic injuries whilst playing sport or who were conscious and did not have major extra-abdominal injuries or clear evidence of other intra-abdominal injury could possibly have been managed expectantly. Such a policy might have avoided splenectomy in a substantial number of cases and thus have eliminated the risk of Overwhelming Post-Splenectomy Infection (OPSI) in these patients.

Effects of alpha-adrenoceptor agonists and antagonists on metabolic rate in cattle.

Brahman steers (Bos indicus) were treated with the alpha 2-adrenergic agonists, guanfacin.HCl (4-440 micrograms/kg), UK14304.HCl (20-125 micrograms/kg) and clonidine.HCl (0.2-5 micrograms/kg). All three agonists produced dose-dependent reductions in metabolic rate, heart rate and rectal temperature (P < 0.001). Brahman heifers were infused with idazoxan.HCl (10 micrograms/kg/hr), an alpha 2-adrenergic antagonist, alone and in combination with an intramuscular injection of guanfacin.HCl (80 micrograms/kg). Idazoxan alone did not alter rectal temperature but it blocked the guanfacin-induced lowering of rectal temperature (P = 0.05 for the interaction between the two drugs). Idazoxan alone raised metabolic rate (P = 0.01). Guanfacin lowered metabolic rate (P = 0.007) and heart rate (P = 0.03), but the blocking of the guanfacin effect by idazoxan could not be demonstrated (P > 0.05) for either. The same heifers treated with 0.5, 1.0 and 5 micrograms/kg prazosin.HCl, an alpha 1-adrenergic antagonist, had significant changes in metabolic rate (P = 0.003) and heart rate (P = 0.008) at 0.5 and 5 micrograms/kg. Metabolic rate and heart rate decreased at the lower dose and increased at the higher dose. These results with cattle parallel previous results in rats (Gazzola, 1993) where a minimal, conceptual model for the partial control of resting metabolic rate by the sympathetic nervous system was postulated. The model indicates points of control in the sympathetic nervous system which could be manipulated so as to alter the metabolic rate of farm animals.

Effects of guanfacin and nitroprusside on the haemodynamics and oxygen consumption of Brahman steers.

1. The systemic vascular resistance (SVR) and oxygen consumption of high grade Brahman (Bos indicus) steers were measured before and after treatment with guanfacin and nitroprusside to test whether the decreased whole-body oxygen consumption seen with guanfacin treatment is due to less oxygen consumption by vascular smooth muscle. 2. Guanfacin changed oxygen consumption by -31% but raised SVR by 61%. Nitroprusside had no significant effect on oxygen consumption but changed SVR by -20%. Moreover, with guanfacin, the changes in oxygen consumption and SVR were temporally incongruent. 3. We conclude that the lowered whole-body oxygen consumption caused by guanfacin was not due to decreased consumption by vascular tissue.

Faecal incontinence: manometric and radiological changes following postanal repair.

Ten patients with idiopathic faecal incontinence underwent postanal repair based on clinical assessment of their symptoms. Their manometric and radiological values before surgery were compared with values from 10 normal volunteers and then the changes following surgery were examined and correlated with the clinical results. Anal manometry was performed using a multilumen, low compliance, perfused catheter system. Anorectal angles and perineal descent were established radiologically. Pre-operative manometry demonstrated significant reduction in maximum and squeeze pressure (median 77 mmHg versus 200 mmHg), the volume required to inhibit the rectoanal reflex (median 40 mL versus 70 mL), and the volume retained in the saline continence test (median 400 mL versus 1500 mL). The majority of patients had obtuse anorectal angles (six of 10 at rest), and abnormal perineal descent (eight of 10 on straining). Nine patients have been improved clinically following surgery. Postoperative manometry and radiology have been performed in seven patients and have shown no significant changes. Anal manometry and radiology are objective means of documenting faecal incontinence although their role in selecting patients for surgery is not yet determined. Postanal repair is effective in restoring continence, although the parameters measured have not explained the mechanism of this effect.

Methane production and energy partition of cattle in the tropics.

The aim of this experiment was to determine CH4 production and energy partition for a range of diets fed to Bos indicus cattle. Six Brahman cattle were fed on three different diets in a replicated Latin square experiment over three periods. The diets were (1) long-chopped Angleton grass (Dicanthium aristatum) hay ad libitum (DM digestibility (DMD) 41 (SE 2)%; 4 g N/kg), (2) long-chopped Rhodes grass (Chloris gayana) hay ad libitum (DMD 60 (SE 1)%; 14 g N/kg) or (3) 2 kg long-chopped lucerne (Medicago sativa) hay/d plus a high-grain diet (ad libitum) (DMD 70 (SE 1)%; 31 g N/kg). CH4 production was measured using confinement-type respiration chambers. Metabolizable energy intake (MJ/d) of cattle fed on Angleton grass (18.4 (SE 2.0)) was lower (P < 0.01) than that for Rhodes grass (54.9 (SE 2.1)), which was lower (P <0.01) than that for the high-grain diet (76.7 (SE 5.8)). CH4 production (g/d) for cattle fed on Rhodes grass (257 (SE 14)) was higher (P < 0.01) than that for cattle fed on both the high-grain diet (160 (SE 24)) and Angleton grass (113 (SE 16)). CH4 conversion rate (MJ CH4 produced per 100 MJ gross energy intake) was not significantly different between cattle fed on Angleton (10.4 (SE 1.1)) and Rhodes (11.4 (SE 0.3)) grass, but was higher (P < 0.01) than for cattle fed on the high-grain diet (6.7 (SE 0.7)). CH4 production (g/kg live-weight gain) was associated (P < 0.001) with both live-weight gain and feed:gain ratio. We conclude that the relationships between CH4 production, energy utilization and live-weight change of cattle fed on tropical forages differ from those of cattle fed on diets based on temperate forages.

A modification of single stapled colorectal anastomosis using the transanal insertion device (TAIS).

A modification of single stapled colorectal anastomosis utilizing a reusable stapler head (transanal insertion device [TAIS]) is described. This modification minimizes the time that the proximal bowel is open by allowing early placement of the circular stapler head, and minimizes the risk of rectal injury that may be associated with the passage of a circular stapling device without the head in situ.

Treatment of advanced ovarian cancer with sequential combination chemotherapy.

Fifty previously untreated patients with advanced or recurrent ovarian cancer (FIGO Stages III and IV) were treated with alternating combination chemotherapy. This consisted of high-dose doxorubicin (70 mg/m2) and cisplatin (100 mg/m2) alternated with CHF (cyclophosphamide, hexamethylmelamine, and 5-fluorouracil). Toxicity (myelosuppression, nephropathy, and neuropathy) was infrequent and mild. Clinical response rates were high (94% response, 62% complete clinical response), but the majority of patients had residual intraabdominal disease at second-look surgery (75%). Thirteen patients (26%) are alive after 4 years of observation (minimum follow-up). Survival was adversely influenced in patients who were older than 70, had Stage IV disease, residual tumor bulk greater than 2 cm, and who failed to achieve complete clinical remission. The median duration of survival (28 months) and percentage of long-term survivors appear similar to that in other platinum-based chemotherapy studies. Although the role of alternating combination chemotherapy in epithelial ovarian cancer remains undefined, it is likely that an alternate approach will be necessary to markedly improve survival rates for patients with this disease.