Further studies on hepatic stimulatory substance (SS) after partial hepatectomy

The stimulatory substance (SS) that is found in the cytosol of regenerating dog livers and which promoted regeneration when injected into the portal vein after Eck fistula did not cause glomerular proliferation when active cytosol was injected into the renal artery. The finding was compatible with but did not prove organ specificity of hepatic SS. The development of SS was completely prevented by extirpation of all nonhepatic splanchnic organs at the same time as partial hepatectomy. This finding indicated that SS in the cytosol donors was a feature rather than an initiator of regeneration, and one that depended upon the collaboration of extrahepatic (including splanchnic hepatotrophic) factors. © 1980

Total hepatectomy and liver replacement (orthotopic liver transplantation) for primary hepatic malignancy

There has been a high incidence of tumor recurrence after liver transplantation for primary hepatic malignancy. Nevertheless, a small but significant palliation has been possible with this approach, even in patients who eventually died of recurrence. Two patients with incidental malignancies in their excised livers apparently have been cured. Further gains will be possible only with extremely discriminating selection of prospective recipients. © 1982 Société Internationale de Chirurgie

Effect of antiandrogen flutamide on measures of hepatic regeneration in rats

Male rat liver undergoes a process of demasculinization during hepatic regeneration following partial hepatectomy. The possibility that antiandrogens might potentiate this demasculinization process and in so doing augment the hepatic regenerative response was investigated. Adult male Wistar rats were treated with the antiandrogen flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for three days prior to and daily after a 70% partial hepatectomy. At various times after hepatectomy, the liver remnants were removed and weighed. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured. Prior to surgery, the administration of 5 mg/day flutamide reduced the hepatic cytosolic androgen receptor activity by 98% and hepatic cytosolic estrogen receptor content by 92% compared to that present in vehicle-treated controls. After hepatectomy, however, all differences in sex hormone receptor activity between the treatment groups were abolished. The rate of liver growth after partial hepatectomy in the three groups was identical. Moreover, hepatectomy-induced increases in ornithine decarboxylase activity and thymidine kinase activity were comparable. These data demonstrate that, although flutamide administration initially alters the sex hormone receptor status of the liver, these affects have no effect on the hepatic regenerative response following a partial hepatectomy. © 1989 Plenum Publishing Corporation

Interventions to promote patients and families' involvement in adult intensive care settings: a protocol for a mixed-method systematic review.

BACKGROUND: There has been an identified need for greater patient and family member involvement in healthcare. This is particularly relevant in an intensive care unit (ICU), as the family provides a key communicative and practical link between patient and clinician. Family members have been deemed a positive beneficial influence on ICU care and recovery processes, yet they themselves are often emotionally affected after discharge. There has been no standardised evidenced-based approach which explores research on family member involvement and the range and quality of contributions remain unclear. This project will undertake a systematic review to assess the evidence base for interventions designed to promote patient and family member involvement in adult intensive care settings and develop a comprehensive typology of interventions for use by clinicians, patients and carers. METHODS: The following databases will be searched without date restriction: MEDLINE, EMBASE and CINAHL, as well as the Cochrane Central Register of Controlled Trials, Joanna Briggs and Cochrane Libraries. Manual searches of recent back issues of leading ICU and patient experience journals will also be undertaken, as will the reference lists of included studies. Unpublished literature will be sought through grey literature databases, including GreyLit and OpenGrey. All evaluation studies that consider intervention activities to promote patient and family member involvement in adult ICUs will be included; all research designs will be eligible. We will seek to include studies that report on a mixture of relevant outcomes for patients and family members. Abstracts and papers will be independently screened by at least two members of the team to determine their inclusion. Included papers will be assessed for methodological rigour using a standard rating approach, which assesses 'quality of study' and 'quality of information'. Quality assessment will be completed by at least two members of the team. Data on interventions, evaluation methods and outcomes will be collated using a predetermined extraction table. These are likely to be heterogeneous in nature, which will mean that the review will follow a narrative approach to synthesis. DISCUSSION: The review will provide valuable and rigorous insight into the range and quality of interventions available to promote patient and family member involvement in ICU. This is the first step towards addressing the absence of a synthesis of research for this context, and will, in addition, develop a typology of available interventions that will help service users and clinicians make informed decisions about the approaches to patient and family member involvement which they might want to adopt. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42018086325)

Cyber security fear appeals:unexpectedly complicated

Cyber security researchers are starting to experiment with fear appeals, with a wide variety of designs and reported efficaciousness. This makes it hard to derive recommendations for designing and deploying these interventions. We thus reviewed the wider fear appeal literature to arrive at a set of guidelines to assist cyber security researchers. Our review revealed a degree of dissent about whether or not fear appeals are indeed helpful and advisable. Our review also revealed a wide range of fear appeal experimental designs, in both cyber and other domains, which confirms the need for some standardized guidelines to inform practice in this respect. We propose a protocol for carrying out fear appeal experiments, and we review a sample of cyber security fear appeal studies, via this lens, to provide a snapshot of the current state of play. We hope the proposed experimental protocol will prove helpful to those who wish to engage in future cyber security fear appeal research

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Combined protein and calcium β-hydroxy-β-methylbutyrate induced gains in leg fat free mass: a double-blinded, placebo-controlled study

Background The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) is widely used as an ergogenic supplement to increase resistance-training induced gains in fat free mass (FFM) and strength in healthy adults. Recent studies have questioned the effectiveness of HMB, particularly when a high protein diet is habitually consumed. To investigate the additive resistance-training induced effects of HMB and protein in untrained individuals, we conducted a randomized double-blind, placebo-controlled study that compared the effects of combined protein and HMB supplementation to protein supplementation alone on FFM and muscle strength after 12-week resistance training. Methods Sixteen healthy men (22 +/- 2 yrs) performed a periodized resistance-training program for twelve weeks (four sessions per week). The program comprised two mesocycles, characterized by a linear periodization and non-linear periodization, respectively, and separated by a 1-week tapering period. All participants received 60 g of whey protein on training days and 30 g of whey protein (WP) on non-training days. Participants were randomly assigned to additionally receive 3 g of calcium HMB (WP + HMB) or a placebo (WP + PLA). Body composition and physical fitness were tested before and after the 12-week training program. Whole-body and arm and leg fat free mass (FFM) were assessed by bioimpedance spectroscopy; upper arm and leg fat free cross sectional areas were also quantified using magnetic resonance imaging (MRI); upper and lower body strength were measured by One-repetition maximum (1-RM) bench press and leg press. Results Whole-body and segmental FFM increased in both groups (P < 0.001). However, gains in leg FFM were higher in WP + HMB vs. WP + PLA (arm FFM: + 6.1% vs. + 9.2%, P = 0.2; leg FFM: + 14.2% vs. + 7.0%, P < 0.01). No change in fat mass was observed (P = 0.59). 1-RM increased in both groups (P < 0.001). Conclusions Combined protein and HMB supplementation resulted in segmental, but not whole-body increases in FFM compared to protein supplementation alone. These findings could explain some of the controversial effects of HMB reported in previous studies and have practical implications for maximizing training-induced gains in FFM and clinical conditions associated with skeletal muscle deconditioning such as aging, sedentary lifestyles, bed rest and spaceflight

Effect of tamoxifen on hepatic regeneration in male rats

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. © 1989 Plenum Publishing Corporation