The mental health of Australians bereaved during the first two years of the COVID-19 pandemic: a latent class analysis.

BACKGROUND: The COVID-19 pandemic disrupted many areas of life, including culturally accepted practices at end-of-life care, funeral rites, and access to social, community, and professional support. This survey investigated the mental health outcomes of Australians bereaved during this time to determine how these factors might have impacted bereavement outcomes. METHODS: An online survey indexing pandemic and bereavement experiences, levels of grief, depression, anxiety, and health, work, and social impairment. Latent class analysis (LCA) was used to identify groups of individuals who shared similar symptom patterns. Multinomial regressions identified pandemic-related, loss-related, and sociodemographic correlates of class membership. RESULTS: 1911 Australian adults completed the survey. The LCA identified four classes: low symptoms (46.8%), grief (17.3%), depression/anxiety (17.7%), and grief/depression/anxiety (18.2%). The latter group reported the highest levels of health, work, and social impairment. The death of a child or partner and an inability to care for the deceased due to COVID-19 public health measures were correlated with grief symptoms (with or without depression and anxiety). Preparedness for the person's death and levels of pandemic-related loneliness and social isolation differentiated all four classes. Unemployment was associated with depression/anxiety (with or without grief). CONCLUSIONS: COVID-19 had profound impacts for the way we lived and died, with effects that are likely to ricochet through society into the foreseeable future. These lessons learned must inform policymakers and healthcare professionals to improve bereavement care and ensure preparedness during and following future predicted pandemics to prevent negative impacts.

The prevalence and impact of depression and anxiety in cardiac rehabilitation: A longitudinal cohort study.

BACKGROUND: Co-morbid depression and anxiety symptoms are frequently under-recognised and under-treated in heart disease and this negatively impacts self-management. AIMS: The purpose of this study was to determine the prevalence, correlates and predictors of depression and anxiety in cardiac rehabilitation programmes, the impact of cardiac rehabilitation on moderate depression, anxiety and stress symptoms, and the relationship between moderate depression, anxiety and stress symptoms and cardiac rehabilitation adherence. METHODS: This was a retrospective cohort study of 5908 patients entering cardiac rehabilitation programmes from 2006-2017, across two Sydney metropolitan teaching hospitals. Variables included demographics, diagnoses, cardiovascular risk factors, medication use, participation rates, health status (Medical Outcomes Study Short Form-36) and psychological health (Depression Anxiety Stress Scales) subscale scores. RESULTS: Moderate depression, anxiety or stress symptoms were prevalent in 18%, 28% and 13% of adults entering cardiac rehabilitation programmes, respectively. Adults with moderate depression (24% vs 13%), anxiety (32% vs 23%) or stress (18% vs 10%) symptoms were significantly less likely to adhere to cardiac rehabilitation compared with those with normal-mild symptoms (p < 0.001). Anxiety (odds ratio 4.395, 95% confidence interval 3.363-5.744, p < 0.001) and stress (odds ratio 4.527, 95% confidence interval 3.315-6.181, p < 0.001) were the strongest predictors of depression. Depression (odds ratio 3.167, 95% confidence interval 2.411-4.161) and stress (odds ratio 5.577, 95% confidence interval 4.006-7.765, p < 0.001) increased the risk of anxiety on entry by more than three times, above socio-demographic factors, cardiovascular risk factors, diagnoses and quality of life. CONCLUSION: Monitoring depression and anxiety symptoms on entry and during cardiac rehabilitation can assist to improve adherence and may identify the need for additional psychological health support. Exploring the relevance and use of adjunct psychological support strategies within cardiac rehabilitation programmes is warranted.

A pragmatic comparative study of palliative care clinician's reports of the degree of shadowing visible on plain abdominal radiographs.

The assessment of constipation symptoms is based on history and physical examination. However, the experience is highly subjective perhaps explaining why palliative medicine doctors continue to use plain abdominal radiographs as part of routine assessment of constipation. Previous studies have demonstrated poor agreement between clinicians with this work in palliative care, limited further by disparity of clinicians' experience and training. The aim of this work was to explore whether there was less variation in the assessments of faecal shadowing made by more experienced clinicians compared to their less experienced colleagues. This pragmatic study was conducted across six palliative care services in Sydney (NSW, Australia). Doctors of varying clinical experience were asked to independently report their opinions of the amount of shadowing seen on 10 plain abdominal radiographs all taken from cancer patients who self-identified themselves as constipated. There were 46 doctors of varying clinical experience who participated including qualified specialists, doctors in specialist training and lastly, doctors in their second- and third post-graduate years. Poor agreement was seen between the faecal shadowing scores allocated by doctors of similar experience and training (Fleiss's kappa (FK): RMO 0.05; registrar 0.06; specialist 0.11). Further, when the levels of agreement between groups were considered, no statistically significant differences were observed. Although the doctors did not agree on the appearance of the film, the majority felt they were able to extrapolate patients' experiences from the radiograph's appearance. As it remains challenging in palliative care to objectively assess and diagnose constipation by history and imaging, uniform and objective assessment and diagnostic criteria are required. It is likely that any agreed criteria will include a combination of imaging and history. The results suggest the use of radiographs alone to diagnose and assess constipation in palliative care represents low value care.

Clinicians' perceptions of medication errors with opioids in cancer and palliative care services: a priority setting report.

This paper reports the findings of a priority setting process, undertaken with cancer and palliative care clinicians, to better understand the characteristics of medication errors with opioids within their services. Participants representing six public hospitals in one Australian state took part in a series of priority setting workshops and, drawing on actual incidents occurring in their services, sought to identify where in the opioid medication process errors were most frequently occurring. Opioid error types and perceived contributing factors were explored, and strategies to reduce/prevent opioid errors were proposed. The priority setting process provided valuable insights into the types of opioid errors that occur in cancer and palliative care services and the complexity of addressing opioid errors from the clinician's perspective. The findings from this priority setting process will inform future targeted quality improvement initiatives to support safe opioid medication practices in cancer and palliative care services.

Family behaviours that have an impact on the self-management activities of adults living with Type 2 diabetes: a systematic review and meta-synthesis.

AIMS: To identify family behaviours that adults with Type 2 diabetes' perceive as having an impact on their diabetes self-management. BACKGROUND: Research suggests that adults with Type 2 diabetes perceive that family members have an important impact on their self-management; however, it is unclear which family behaviours are perceived to influence self-management practices. METHODS: This meta-synthesis identified and synthesized qualitative studies from the databases EMBASE, Medline and CINAHL published between the year 2000 and October 2016. Studies were eligible if they provided direct quotations from adults with Type 2 diabetes, describing the influence of families on their self-management. This meta-synthesis adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. RESULTS: Of the 2606 studies screened, 40 were included. This meta-synthesis identified that adults with Type 2 diabetes perceive family behaviours to be either: 1) facilitators of diabetes self-management; 2) barriers to diabetes self-management; or 3) equivocal behaviours with the potential to both support and/or impede diabetes self-management. Seven sub-themes were identified within these themes, including: four facilitator sub-themes ('positive care partnerships'; 'family watchfulness'; 'families as extrinsic motivator' and 'independence from family'); two barrier sub-themes ('obstructive behaviours' and 'limited capacity for family support'); and one equivocal behaviours subtheme ('regular reminders and/or nagging'). CONCLUSION: While most family behaviours are unambiguously perceived by adults with Type 2 diabetes to act as facilitators of or barriers to self-management, some behaviours were perceived as being neither clear facilitators nor barriers; these were termed 'equivocal behaviours'. If the concept of 'equivocal behaviours' is confirmed, it may be possible to encourage the adult living with Type 2 diabetes to reframe these behaviours so that they are perceived as enabling their diabetes self-management.

A single pipeline embolization device is sufficient for treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: The Pipeline Embolization Device has emerged as an important treatment option for intracranial aneurysms. The number of devices needed to treat an aneurysm is uncertain and is the subject of vigorous debate. The purpose of this study was to compare rates of complications, aneurysm occlusion, and outcome in patients treated with a single-versus-multiple Pipeline Embolization Devices. MATERIAL AND METHODS: One hundred seventy-eight patients were treated with the Pipeline Embolization Device at our institution. Patients were divided into 2 groups: a single-device group (n = 126) and a multiple-device group (n = 52). RESULTS: There was no statistically significant difference between the 2 groups with respect to baseline characteristics except for age and aneurysm size (higher with multiple Pipeline Embolization Devices). Complications occurred more frequently with multiple (15%) versus a single device (5%, P = .03). In multivariate analysis, the use of multiple devices independently predicted complications. A similar proportion of patients achieved adequate aneurysm obliteration at follow-up in the single-device (84%) and the multiple-device groups (87%, P = .8). In multivariate analysis, age and follow-up time predicted obliteration. At follow-up, a significantly higher proportion of patients treated with a single device (97%) achieved a favorable outcome compared with those treated with multiple devices (89%, P = .03). In multivariate analysis, there was a strong trend for the use of a single device to predict favorable outcomes (P = .06). CONCLUSIONS: Treatment with a single Pipeline Embolization Device provides similar occlusion rates with less complications and better overall outcomes. These findings suggest that a single Pipeline Embolization Device is sufficient for treatment of most intracranial aneurysms.

Systemic bias in the medical literature on androgen deprivation therapy and its implication to clinical practice.

BACKGROUND: LHRH agonists are used for androgen deprivation therapy (ADT) to treat prostate cancer, but have many side effects that reduce of the quality of life of prostate cancer patients and their partners. Patients are poorly informed about the side effects of these drugs and how to manage them. AIM: To test the hypothesis that there is bias in the peer-reviewed literature on ADT that correlates with an association between authors and the luteinising hormone-releasing hormone (LHRH) agonists pharmaceutical industry. METHODS: We assessed 155 articles on ADT published in English-language peer-reviewed journals in terms of how comprehensive they were in acknowledging LHRH agonists' side effects. RESULTS: Although the literature regarding ADT is substantial, the vast majority of articles failed to acknowledge many of the more stressful side effects of ADT for patients and their partners. Articles most likely to acknowledge the psychosocial impact of ADT were significantly less likely to have had industrial support than those articles that did not mention those side effects. Alternative treatments to the LHRH agonists were rarely mentioned. Authors who indicated some association with a pharmaceutical company tended to minimise the side effects of LHRH agonists and not acknowledge alternatives to the LHRH agonists for ADT. CONCLUSION: Industrial support is associated with a proliferation of articles published in the peer-reviewed literature directed at practising physicians. Such flooding of the literature may, in part, limit physicians' knowledge of the side effects of these drugs and, in turn, account for the poor knowledge that patients on LHRH agonists have about the drugs they are taking and ways to manage their side effects.

Electromagnetic fields and DNA damage.

A major concern of the adverse effects of exposure to non-ionizing electromagnetic field (EMF) is cancer induction. Since the majority of cancers are initiated by damage to a cell's genome, studies have been carried out to investigate the effects of electromagnetic fields on DNA and chromosomal structure. Additionally, DNA damage can lead to changes in cellular functions and cell death. Single cell gel electrophoresis, also known as the 'comet assay', has been widely used in EMF research to determine DNA damage, reflected as single-strand breaks, double-strand breaks, and crosslinks. Studies have also been carried out to investigate chromosomal conformational changes and micronucleus formation in cells after exposure to EMF. This review describes the comet assay and its utility to qualitatively and quantitatively assess DNA damage, reviews studies that have investigated DNA strand breaks and other changes in DNA structure, and then discusses important lessons learned from our work in this area.

Hormones and honest signals: males with larger ornaments elevate testosterone more when challenged.

When male investment in mating varies with quality, reliable sexual signals may evolve. In many songbirds, testosterone mediates mating investment, suggesting that signals should be linked to testosterone production. However, because testosterone may change rapidly during behaviour such as territorial aggression and courtship, efforts to establish such a relationship have proved challenging. In a population of dark-eyed juncos, we measured individual variation in the production of short-term testosterone increases by injecting gonadotropin-releasing hormone (GnRH). We found a positive correlation between the magnitude of these increases and the size of a plumage ornament ('tail white') previously shown to be important for female choice and male-male competition. We then measured naturally elevated testosterone levels produced during male-male competition and found that they covaried with those induced by GnRH. We suggest that the association between tail white and testosterone increases may allow conspecifics to assess potential mates and competitors reliably using tail white.

Comment on "The Brain of LB1, Homo floresiensis".

Endocast analysis of the brain Homo floresiensis by Falk et al. (Reports, 8 April 2005, p. 242) implies that the hominid is an insular dwarf derived from H. erectus, but its tiny cranial capacity cannot result from normal dwarfing. Consideration of more appropriate microcephalic syndromes and specimens supports the hypothesis of modern human microcephaly.

The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis.

Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 unique targets on a 6.5K cDNA microarray, approximately 3% were subject to modification in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and cyclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, which showed decreased expression. Thirty % of expression changes occurred in regions the genomic copy number of which remained balanced. Of the remainder, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A relative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically significant increase or decrease, respectively, in the average expression level of all of the genes on the chromosome. However, of these genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some instances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpressed by > or =1.7-fold when scored individually. Cluster analysis by gene function suggests that prostate tumorigenesis in these cell line models involves alterations in gene expression that may favor invasion, prevent apoptosis, and promote growth.

The genetic basis of renal epithelial tumors: advances in research and its impact on prognosis and therapy.

The genetics of renal cell carcinoma continues to elucidate the pathways of kidney tumorigenesis. The relationship between the VHL gene and clear cell carcinoma, MET and papillary carcinoma, and the families of genes that they regulate, continues to be unraveled. New hereditary kidney cancer syndromes, like familial oncocytoma and the Birt-Hogg-Dubé syndrome, have been identified and the search for the genes that cause them is under way. Researching the genetics of these disorders is essential for an understanding of sporadic kidney cancer genetics. This chapter will review the current knowledge of the hereditary kidney cancer syndromes, the genes that cause them, new advances in genetic research and techniques, and how this information impacts upon diagnostic, prognostic, and therapeutic methods of the future.

Molecular cytogenetic characterization of early and late renal cell carcinomas in von Hippel-Lindau disease.

Deletions of 3p25, gains of chromosomes 7 and 10, and isochromosome 17q are known cytogenetic aberrations in sporadic renal cell carcinoma (RCC). In addition, a majority of RCCs have loss of heterozygosity (LOH) of the Von Hippel-Lindau (VHL) gene located at chromosome band 3p25. Patients who inherit a germline mutation of the VHL gene can develop multifocal RCCs and other solid tumors, including malignancies of the pancreas, adrenal medulla, and brain. VHL tumors follow the two-hit model of tumorigenesis, as LOH of VHL, a classic tumor suppressor gene, is the critical event in the development of the neoplastic phenotype. In an attempt to define the cytogenetic aberrations from early tumors to late RCC further, we applied spectral karyotyping (SKY) to 23 renal tumors harvested from 6 unrelated VHL patients undergoing surgery. Cysts and low-grade solid lesions were near-diploid and contained 1-2 reciprocal translocations, dicentric chromosomes, and/or isochromosomes. A variety of sole numerical aberrations included gains of chromosomes 1, 2, 4, 7, 10, 13, 21, and the X chromosome, although no tumors had sole numerical losses. Three patients shared a breakpoint at 2p21-22, and three others shared a dicentric chromosome 9 or an isochromosome 9q. In contrast to the near-diploidy of the low-grade lesions, a high-grade lesion and its nodal metastasis were markedly aneuploid, revealed loss of VHL by fluorescence in situ hybridization (FISH), and contained recurrent unbalanced translocations and losses of chromosome arms 2q, 3p, 4q, 9p, 14q, and 19p as demonstrated by comparative genomic hybridization (CGH). By combining SKY, CGH, and FISH of multiple tumors from the same VHL kidney, we have begun to identify chromosomal aberrations in the earliest stages of VHL-related renal cell tumors. Our current findings illustrate the cytogenetic heterogeneity of different VHL lesions from the same kidney, which supports the multiclonal origins of hereditary RCCs. Published 2001 Wiley-Liss, Inc.

The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the "different disease" hypothesis.

BACKGROUND: A high proportion of U.S. patients with gastric carcinoma do not receive surgical treatment. To sharpen staging criteria and facilitate comparisons with surgical series, an analysis of patients whose treatment included gastrectomy was undertaken. In addition, to evaluate the "different disease" hypothesis as an explanation for superior Japanese results, outcomes for Japanese Americans were examined. METHODS: Data were obtained from National Cancer Data Base (NCDB) reports of 50,169 gastric carcinoma cases diagnosed during the years 1985-1996 and treated with gastrectomy. In addition to demographic and treatment information, 5-year and 10-year relative survival rates are presented, with stage defined according to fifth edition American Joint Committee on Cancer (AJCC) staging procedures. RESULTS: Stage-stratified 5-year and 10-year relative survival rates were as follows: Stage IA, 78%/65%; Stage IB, 58%/42%; Stage II, 34%/26%; Stage IIIA, 20%/14%; Stage IIIB, 8%/3%; and Stage IV, 7%/5%. Stage-stratified survival for Japanese Americans was higher. Males had a poorer prognosis than females, and the male-to-female ratio for Japanese Americans was lower. Proximal tumors were associated with a worse prognosis than distal tumors; the proportion of Japanese Americans with proximal disease was less than in the overall patient group. Japanese Americans underwent resection of adjacent organs less frequently. In this series, adjuvant therapy did not substantially affect survival. Overall, 20% were 10-year survivors; of these, 67% were lymph node negative and 98% had /= 15 lymph nodes analyzed. Stage migration was evident in cases with

Predictive value of preoperative tests in discriminating bilateral adrenal hyperplasia from an aldosterone-producing adrenal adenoma.

In primary hyperaldosteronism, discriminating bilateral adrenal hyperplasia (BAH) from an aldosterone-producing adenoma (APA) is important because adrenalectomy, which is usually curative in APA, is seldom effective in BAH. We analyzed the results from our most recent 7-yr series to evaluate the predictive value of preoperative noninvasive tests compared with adrenal vein sampling (AVS). Forty-eight patients with hypertensive hyperaldosteronism underwent bedside testing, computed tomography (CT) imaging, and AVS. Those in whom the results of AVS indicated APA underwent adrenalectomy. Twelve (30%) and 14 (34%) of 41 patients with APA had paradoxical falls with ambulation in plasma aldosterone concentration (PAC) and 18-hydroxycorticosterone (18-OH-B), respectively. Twenty-nine (70%) and 26 (65%) APA patients had a rise in PAC and 18-OH-B, respectively, as did all 8 BAH patients. Significant identifiers of BAH were supine PAC values less than 15 ng/dL (P: = 0.04), an increase greater than 60% (P: = 0.02) in PAC with ambulation, and supine 18-OH-B values less than 60 ng/dL (P: = 0.04). CT imaging alone was not predictive for BAH or APA. In our population, patients with a positive bedside test result (e.g. a fall in PAC and/or 18-OH-B) and a unilateral adrenal nodule on CT (10 of 41 patients) could have proceeded directly to adrenalectomy for APA. However, a positive bedside test result with a negative CT or a negative bedside test result regardless of CT findings required AVS to confirm the diagnosis and site of disease.

Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report.

BACKGROUND: Primary lung cancer accounts for approximately 14% of all new cancers and 28% of cancer deaths in the U.S. Previous reviews have shown limited progress in the management or outcome of this devastating disease. METHODS: Reports described in the current study were 713,043 primary lung malignancies diagnosed between 1985 and 1995 and submitted to the National Cancer Data Base. Demographic, tumor, and treatment patterns for 1995 were compared with those for 1985-1987, 1988-1991, and 1992-1994. Ten-year relative survival rates were presented for selected demographic and histologic groups and 5-year relative survival rates were presented by stage and dominant treatment modalities for major carcinoma histologies. RESULTS: Previously observed demographic trends were evident, with increasing proportions of patients being older, female, and African American, and more cases reported to be adenocarcinomas. There was a substantial shift toward more complete staging but no change in the distribution of staged cases. Compared with earlier patients, fewer 1995 patients received cancer-directed treatment. More surgical patients underwent lymph node dissection, and radiation treatment was supplemented more often with chemotherapy. The overall 10-year relative survival rate was 7%. The 5-year survival for American Joint Committee on Cancer Stage I surgical patients was >50% for all nonsmall cell histologic groups. CONCLUSIONS: Recent shifts in treatment, although minimal, are consistent with current literature concerning the effectiveness of lung carcinoma treatment. The authors believe that the overall poor survival of lung carcinoma patients points to a continuing need for improved prevention and treatment measures. The comparatively superior survival of Stage I nonsmall cell lung carcinoma surgical patients indicates that a substantial number of patients have the potential to be treated successfully.

Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.

We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.

A survey of hospital management practices for vulvar melanoma.

BACKGROUND: Vulvar melanoma is a very rare form of cancer. The purpose of this study was to describe practice patterns for the management of vulvar melanoma. STUDY DESIGN: The National Cancer Data Base was reviewed from 1985 through 1994 for patient reports submitted with a diagnosis of vulvar melanoma. RESULTS: Five hundred sixty-nine patients with vulvar melanoma were identified. A substantial number of patients were older; during the latter period of this study (1990 to 1994), 50% were 70 years old or older. Surgery was used in more than 90% of patients with stages 0 to III. Local excision was used mainly in early-stage (0 and I) disease. Adjuvant therapy was used infrequently. Lymph node evaluation was performed in more than half of the patients, with greater frequency for patients who had advanced disease. The overall 5-year relative survival rate was 62%. If the lymph nodes contained metastases, survival was poor. Patients with recurrent disease also had poor survival. CONCLUSIONS: Surgery remains the mainstay of therapy for vulvar melanoma. The use of excision and radical operations remained constant during the 10 years of the study.

The effect of nutritional and hormonal supplementation on protein synthesis immediately after liver transplantation.

We have previously shown that immediately after liver transplantation (LT) the porcine recipient exhibits elevated plasma glucagon, increased fractional synthetic rate (FSR) of fibrinogen, and decreased FSR of fixed or structural liver proteins. The purpose of this study was to evaluate the effect of nutritional and hormonal supplementation on these observations 24 h after LT. Two groups of nine pigs were studied 1 day after LT using radioisotopic and arteriovenous difference techniques. A control group underwent LT with saline infusion and a supplemented group underwent LT with infusion of glucose, amino acids (6 and 1.06 mg/kg. min, respectively), and intraportal insulin (0.6 mU/kg. min) and glucagon (1.3 ng/kg. min). Primed constant infusions of [3H]leucine were used to determine leucine flux, an estimate of whole body protein breakdown, and fractional synthetic rates (FSR). The following changes were noted with supplementation: elevated plasma insulin (6 +/- 1 versus 29 +/- 4 microU/ml, control versus supplemented, respectively, P < 0.05), decreased glucagon to normal levels (323 +/- 65 versus 102 +/- 12 pg/ml, P < 0.05), decreased fibrinogen FSR (108 +/- 15 versus 70 +/- 6%/day, P < 0.025), and increased fixed liver protein FSR (8 +/- 1 versus 13 +/- 2%/day, P < 0.05, respectively). Albumin FSR was unaltered by supplementation (8 +/- 2 versus 6 +/- 1%/day, respectively). Nutritional and hormonal supplementation immediately after LT restored the measured protein synthesis in the allograft to near normal levels 1 day after transplantation.