Commonwealth Serum Laboratories Research Articles

100 years flashback

100 years flashback

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

First-Line Treatment with Ibrutinib (Ibr) Plus Venetoclax (Ven) for Chronic Lymphocytic Leukemia (CLL): 2-Year Post-Randomization Disease-Free Survival (DFS) Results from the Minimal Residual Disease (MRD) Cohort of the Phase 2 Captivate Study

First-Line Treatment with Ibrutinib (Ibr) Plus Venetoclax (Ven) for Chronic Lymphocytic Leukemia (CLL): 2-Year Post-Randomization Disease-Free Survival (DFS) Results from the Minimal Residual Disease (MRD) Cohort of the Phase 2 Captivate Study

Comparative Effectiveness of SGLT2i Versus DPP4i on Cardiovascular, Kidney and Hyperkalemia Outcomes in Individuals from Routine Clinical Practice: Observational Cohort Study

Background: While clinical trials have demonstrated efficacy for SGLT2 inhibitors (SGLT2i) on preventing cardiovascular and kidney damage, few high-quality studies have expanded to routine-care settings of low-risk patients. Previous observational studies were limited by immortal time bias or did not adjust for laboratory measurements. Methods: We compared clinical outcomes of adults who started SGLT2i or DPP4i therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HHF). Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, atrial fibrillation, hyperkalemia and kidney disease progression (composite kidney failure and doubling of serum creatinine). Propensity score weighted Cox regression was used to estimate hazard ratios and balance 56 covariates. Results: We included 16,537 individuals (5526 SGLT2i; 11,011 DPP4i users), followed for median 1.9 years. Median age was 64 years (36% women), median estimated glomerular filtration rate 87 ml/min/1.73m2 and 31% had albuminuria. After weighting, patients starting SGLT2i therapy were at lower risk for the composite of CV death/HHF (HR 0.65; 95% CI 0.47-0.89) and hyperkalemia (HR 0.41; 95% CI 0.20-0.83) compared with DPP4i, without an increase in hypokalemia (HR 0.98; 95% CI 0.72-1.34). The adjusted HRs (95% CI) were 0.82 (0.64-1.06) for MACE, 0.74 (0.52-1.06) for all-cause mortality, 0.95 (0.68-1.33) for atrial fibrillation and 0.54 (0.27-1.08) for kidney disease progression. Conclusions: SGLT2i use compared with DPP4i was associated with a reduction in cardiovascular and kidney outcomes similar in magnitude to trials, as well as a lower risk of hyperkalemia. Funding: Research reported in this publication was supported by the Swedish Research Council (#2019-01059), the Swedish Heart and Lung Foundation and the Westman Foundation. ELF acknowledges support by a Rubicon Grant of the Netherlands Organization for Scientific Research (NWO). Declaration of Interests: JC acknowledges consultancy for Baxter and AstraZeneca, and grant support to Karolinska Institutet from AstraZeneca, Viforpharma and Astellas, all outside the submitted work. CMC has received consultation, advisory board membership or research funding from the Ontario Ministry of Health, Sanofi, Johnson & Johnson, Pfizer, Leo Pharma, Astellas, Janssen, Amgen, Boehringer-Ingelheim and Baxter, all outside the submitted work. None of the other authors declare relevant financial interests that would represent a conflict of interest. MJJ is responsible for research programs that have received unrestricted funding from Gambro, Baxter, Commonwealth Serum Laboratories (CSL), Amgen, Eli Lilly, and Merck; has served on advisory boards and steering committees sponsored by Akebia, Baxter, Boehringer Ingelheim, CSL, Janssen, and Vifor; and spoken at scientific meetings sponsored by Janssen, Amgen, and Roche, with any consultancy, honoraria, or travel support paid to her institution. Ethics Approval Statement: The study utilized only de-identified data and thus was deemed not to require informed consent, being approved by the regional ethical review boards and the Swedish National Board of Welfare.

Using Ibrutinib in Earlier Lines of Treatment Results in Better Outcomes for Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Using Ibrutinib in Earlier Lines of Treatment Results in Better Outcomes for Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Does industry-sponsored education foster overdiagnosis and overtreatment of depression, osteoporosis and over­active bladder syndrome? An Australian cohort study

ObjectivesTo investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment.Design and settingThis retrospective cohort study examines publicly reported...

Thorburn Brailsford Robertson: Brilliant Scientist, Innovator and Australia’s First Professor of Biochemistry

Thorburn Brailsford Robertson (1884–1930) was educated in Adelaide and held appointments at the University of California, Berkeley (where he completed his PhD in 1907), and the University of Toronto before taking up his appointment at Adelaide in 1919 as Australia's first Professor of Biochemistry. In his research on the biochemical basis of growth and senescence he discovered in pituitary tissue a growth factor he called Tethelin. He made important contributions to the fabric and collegiality of the University of Adelaide. Amongst his many scientific contributions he was the first person outside Canada to prepare insulin, a project taken up by the Commonwealth Serum Laboratories. In 1927 he became the first Chief of the Division of Animal Nutrition in the Council for Scientific and Industrial Research, for whom he investigated sheep nutrition and wool growth.

Clinical and Diagnostic Developments of a Gamma Interferon Release Assay for Use in Bovine Tuberculosis Control Programs

Currently, the Bovigam assay is used as an official supplemental test within bovine tuberculosis control programs. The objectives of the present study were to evaluate two Mycobacterium bovis-specific peptide cocktails and purified protein derivatives (PPDs) from two sources, liquid and lyophilized antigen preparations. PPDs and peptide cocktails were also used for comparison of a second-generation gamma interferon (IFN-γ) release assay kit with the currently licensed first-generation kit (Bovigam; Prionics AG). Three strains of M. bovis were used for experimental challenge: M. bovis 95-1315, M. bovis Ravenel, and M. bovis 10-7428. Additionally, samples from a tuberculosis-affected herd (i.e., naturally infected) were evaluated. Robust responses to both peptide cocktails, HP (PC-HP) and ESAT-6/CFP10 (PC-EC), and the PPDs were elicited as early as 3 weeks after challenge. Only minor differences in responses to Commonwealth Serum Laboratories (CSL) and Lelystad PPDs were detected with samples from experimentally infected animals. For instance, responses to Lelystad M. avium-derived PPD (PPDa) exceeded the respective responses to the CSL PPDa in M. bovis Ravenel-infected and control animals. However, a 1:4 dilution of stimulated plasma demonstrated greater separation of PPDb from PPDa responses (i.e., PPDb minus PPDa) with the use of Lelystad PPDs, suggesting that Lelystad PPDs provide greater diagnostic sensitivity than CSL PPDs. The responses to lyophilized and liquid antigen preparations did not differ. Responses detected with first- and second-generation IFN-γ release assay kits (Bovigam) did not differ throughout the study. In conclusion, antigens may be stored in a lyophilized state without loss in potency, PC-HP and PC-EC are dependable biomarkers for aiding in the detection of bovine tuberculosis, and second-generation Bovigam kits are comparable to currently used kits.

Cervical Cancers After Human Papillomavirus Vaccination

Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Medical University Vienna, Vienna, Austria (Joura) Royal Women’s Hospital and Royal Children’s Hospital Melbourne, University of Melbourne, Melbourne, Australia (Garland) Financial Disclosure: Dr. Joura conducted a human papillomavirus trial and received funding through his institution from Merck (Whitehouse Station, NJ) and GlaxoSmithKline (Rixensart, Belgium). He has also received lecture fees from Merck, GlaxoSmithKline, and Sanofi Pasteur MSD (Lyon, France). Dr. Garland has received advisory fees and grant support from Common-wealth Serum Laboratories (Victoria, Australia) and GlaxoSmithKline and lecture fees from Merck and GlaxoSmithKline. She has also received funding from her institution to conduct vaccine studies for Merck and GlaxoSmithKline. Editor’s Note: The authors declined to respond.

The Birth of the Biotechnology Era: Penicillin in Australia, 1943–80 1

Abstract As Australia and other countries seek to establish biotechnology industries, it is timely to review successes and failures in this field. One of the most notable stories is the development of penicillin, as a wartime project, to which Australians made major contributions. Australians during and immediately after the war contributed much to the scientific identification and purification of penicillin, and to the industrial scaling up in its production at the Commonwealth Serum Laboratories in Melbourne. This was a classic instance of war accelerating innovations in public administration. Yet the nascent antibiotic industry was never allowed to gain international competitiveness, and was allowed to run down and eventually disappeared by the end of the 1970s. This article is concerned to tease out the puzzle posed by this contrast in aspirations, between the highest levels of scientific and technical achievement in bringing penicillin into widespread use (Australia being the first country in the world to provide penicillin to the civilian population in 1944) and shockingly poor performance in sustaining and developing a national antibiotics industry. As the stirrings of a biotechnology industry may be observed in the first decade of the twenty‐first century, it would be unfortunate to ignore the lessons of this earlier experience at the birth of the biotechnology era.

Corrigendum

Emergency Medicine AustralasiaVolume 19, Issue 6 p. 567-567 Free Access Corrigendum This article corrects the following: Stephen's Banded Snake envenomation treated with tiger snake antivenom Michael Hession, Volume 19Issue 5Emergency Medicine Australasia pages: 476-478 First Published online: October 3, 2007 First published: 14 November 2007 https://doi.org/10.1111/j.1742-6723.2007.01046.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat The Editor-in-Chief wishes to make the following corrections to the article: Hession M. Stephen's Banded Snake envenomation treated with tiger snake antivenom. Emerg. Med. Australas. 2007; 19: 476–478. Syntax error changes: Page 476, Abstract, 4th/5th lines: should read ‘. . . reacted to the Tiger Snake Antivenom Indicated Well 1 on the Commonwealth Serum Laboratories Snake Venom Detection Kit’. Page 477, left column, 4th paragraph, lines 4 and 5: should read ‘. . . a definite positive reaction in wells 7 (the control well) and 1.’ Page 477, left column 4th paragraph, line 7: should read ‘. . . genus Hoplocephalus’. Scientific error changes: Page 477, left column, 2nd last paragraph: Tiger snake antivenom is recommended for Stephen's banded snake in addition to the other snakes mentioned. This is contained in the CSL manufacturers insert for the CSL Snake Venom Detection Kit, which states under Interpretation of the Snake Venom Detection test: How to perform a Snake Venom Detection test: “If well 1 changes to blue first, then the patient has been bitten by either a tiger snake or rough scaled snake, or possibly a copperhead, broad-headed snake or Stephen's banded snake. Envenoming from all these snakes respond to CSL Tiger Snake Antivenom. Wells 7 & 1 positive: If systemic effects include defibrination, paralysis +/– myolysis, suggests tiger snake or rough scaled snake bite. If systemic effects defibrination only, consider bite by broad-headed, pale-headed or Stephen's banded snake. If systemic effects confined to paralysis, without defibrination, consider possibility of copperhead bite.” See reference 1 below. Page 477, right column, 2nd paragraph, lines 8 and 9: There is a description of the management of Stephen's Banded envenomation without antivenom use. See reference 2 below. Page 477, right column, last paragraph, lines 2 and 3: There are human reports (of Stephen's Banded Snake envenomation) in the medical literature. See reference 2 below. Page 477, right column, last paragraph, lines 3 and 4: Animal studies on Stephen's banded snake have clearly demonstrated procoagulant activity similar to the Australian tiger snake. See reference 3 below.

Stephen's Banded Snake envenomation treated with tiger snake antivenom

Demonstration of the use of Tiger Snake Anti-venom in Stephen's Banded Snake envenomation is described. The patient presented with a clear history of a bite and a mild headache. Subsequently, the patient developed defibrination coagulopathy. A swab of the bite site reacted to the Tiger Snake Antivenom Indicated Well 1 [corrected] on the Commonwealth Serum Laboratories Snake Venom Detection Kit [corrected] Two ampoules of anti-venom were used. A mild allergic reaction to tiger snake antivenom developed. There was resolution of the coagulopathy.

Twentieth century toxinology and antivenom development in Australia

It was not until the last decade of the 19th century that an experimental approach (led by Bancroft in Queensland and Martin in Sydney and Melbourne) brought a higher plane of scientific objectivity to usher in the modern era of Australian toxinology. This Australia era, 1895–1905, coincided with and in some respects was the result of the new knowledge emerging from Europe and the Americas of the therapeutic effects of antitoxins. The subsequent systematic study of Australian venoms and toxins through to the 1930s and beyond, by Tidswell, Fairley, Ross, Kellaway and Cleland, set the foundation for Australia's leading reputation in venom research. As elsewhere, this development was to revolutionise the medical management of those victims who in the past had died in Australia from our venomous and toxic fauna. Morgan, Graydon, Weiner, Lane and Baxter at the Commonwealth Serum Laboratories emphasised the importance of cooperation between those expert at catching and milking the venomous creatures and those developing the antivenoms. Commercial antivenom manufacture began in Australia in 1930 with the tiger snake antivenom. This was followed by other antivenoms for the other important species (1955: taipan; 1956: brown snake; 1958: death adder; 1959: Papuan black snake; 1961: sea snake; 1962: polyvalent) including the first marine antivenoms in the world (1956: stonefish antivenom; 1970: box jellyfish) culminating, in 1980, with the release of the funnel web spider antivenom. More recent activity has focused on veterinary antivenoms and production of new generation human antivenoms for export (CroFab and ViperaTAB). This paper reviews some of the milestones of Australian toxinology, and antivenom development in particular, during the 20th century.

Struan Sutherland—Doyen of envenomation in Australia

Struan Sutherland (1936–2002) was the doyen of medical research in the field of envenomation and the ultimate authority on the medical management of envenomated victims in Australia for almost 3 decades. In 1981 as Head of Immunology Research of Commonwealth Serum Laboratories (CSL), he produced an antivenom against the Sydney Funnel-web Spider ( Atrax robustus)—an accomplishment that had defied numerous previous attempts. Struan also invented the pressure-immobilisation technique of first-aid for snake bite. This ingenious, simple but safe and effective technique revolutionised first-aid management of snake bite and of some other types of envenomation. It made redundant the use of tourniquets and other dangerous first-aid treatments. Similarly, he helped to develop a snake venom detection kit, which enables doctors working at a victim's bedside to ascertain which snake was responsible and which antivenom should be administered. He had a very wide range of research interests and was a prodigious researcher publishing over 200 scientific and medical articles, numerous chapters in books and the standard Australian medical textbook on the management of envenomation, Australian Animal Toxins. He made major contributions to the understanding of the venoms of Australia's remarkable range of fauna including snakes, spiders, Blue-ringed octopus, ants, jellyfish and stinging fish. Struan served the medical fraternity and the public selflessly. He was always available to doctors, or to anybody, to give advice at any hour of the day or night, on management of envenomated victims. Members of the Australian Venom Research Unit, which he founded in 1994 at The University of Melbourne, now continue this 24-h advisory service.

ATP7B Mediates Vesicular Sequestration of Copper: Insight Into Biliary Copper Excretion

The Wilson protein (ATP7B) regulates levels of systemic copper by excreting excess copper into bile. It is not clear whether ATP7B translocates excess intrahepatic copper directly across the canalicular membrane or sequesters this copper into exocytic vesicles, which subsequently fuse with canalicular membrane to expel their contents into bile. The aim of this study was to clarify the mechanism underlying ATP7B-mediated copper detoxification by investigating endogenous ATP7B localization in the HepG2 hepatoma cell line and its ability to mediate vesicular sequestration of excess intracellular copper. Immunofluorescence microscopy was used to investigate the effect of copper concentration on the localization of endogenous ATP7B in HepG2 cells. Copper accumulation studies to determine whether ATP7B can mediate vesicular sequestration of excess intracellular copper were performed using Chinese hamster ovary cells that exogenously expressed wild-type and mutant ATP7B proteins. In HepG2 cells, elevated copper levels stimulated trafficking of ATP7B to pericanalicular vesicles and not to the canalicular membrane as previously reported. Mutation of an endocytic retrieval signal in ATP7B caused the protein to constitutively localize to vesicles and not to the plasma membrane, suggesting that a vesicular compartment(s) is the final trafficking destination for ATP7B. Expression of wild-type and mutant ATP7B caused Chinese hamster ovary cells to accumulate copper in vesicles, which subsequently undergo exocytosis, releasing copper across the plasma membrane. This report provides compelling evidence that the primary mechanism of biliary copper excretion involves ATP7B-mediated vesicular sequestration of copper rather than direct copper translocation across the canalicular membrane.

ANTIVENOM DEVELOPMENT IN AUSTRALIA

Brown snakes, Pseudonaja genus, cause more bites and deaths to animals and humans in Australia than any other terrestrial snake genus. Some aspects of treatment of brown snakebites with antivenom remain poorly managed due to the apparent inability of the antivenom to counter the prothrombin activator in the venom. We present evidence of a new novel antivenom (Antiven Pty Ltd Brown snake antivenom (ABSAV)), which shows high efficacy in reversing the hemostatic abnormality caused by brown snake envenomation. It is also more efficient at reversing overall toxicity. In clotting tests, it is substantially more potent than Commonwealth Serum Laboratories Ltd (CSL) Brown snake antivenom and is twice as effective in reversing overall toxicity than CSL Brown snake antivenom.Antiven Pty. Ltd. Brown snake antivenom is currently being assessed by the National Registration Authority (veterinary regulative body in Australia).

Cross reactivity between venomous, mildly venomous, and non‐venomous snake venoms with the Commonwealth Serum Laboratories Venom Detection Kit

Studies have noted the relatively common occurrence of positive urine results with the Commonwealth Serum Laboratories Venom Detection Kit (VDK) when testing patients with suspected snakebite who are not envenomed. Possible explanations have been false positive test results or subclinical envenoming. We investigated a third possibility, that there is potential for the venom (or saliva) from mildly venomous and non-venomous snakes to give a positive reading with the VDK. Venoms/saliva from three non-venomous and seven mildly venomous snake species were tested in the laboratory with the VDK, along with control venoms from four of the five major snake genera (Brown snake, Tiger snake, Death adder and Black snake). Two of the venom/saliva samples, from Gould's hooded snake (Parasuta gouldii), a mildly venomous snake, and the Black-headed python (Aspidites melanocephalus), a non-venomous snake, caused a positive test for the tiger snake genus. There was also cross-reactivity between black snake venoms and the tiger snake well of the VDK. This study provides a further possible explanation for 'false positive' VDK results, that is venom/saliva presence or absorption from mildly or non-venomous snakes and cross reactivity with venomous snakes on VDK testing. It has implications for antivenom use should it ever be required for more severe envenoming syndromes from mildly or moderately venomous snakes, and for further research. It reinforces the practice of only using VDK testing in patients who show definite evidence of envenoming.

Translational control of tumor necrosis factor-related apoptosis-inducing ligand death receptor expression in melanoma cells.

In the present study, it was found that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-R2 protein expression did not correlate with mRNA expression in melanoma cell lines. In particular, early passage primary cultures from patients had low TRAIL-R2 protein expression compared with later passage cultures although TRAIL-R2 mRNA expression was similar in early and late passages. Similarly, cell lines made resistant to TRAIL by cultures in TRAIL had low TRAIL-R2 protein expression but normal levels of mRNA for TRAIL-R2. Expression from a luciferase reporter gene construct with the 3'-untranslated region (UTR) (but not the 5'-UTR) of TRAIL-R2 was suppressed when transfected into the TRAIL-selected (resistant) melanoma lines compared with that seen in the parental (sensitive) lines. Similar results were seen in early passage (resistant) cultures compared with late passage (sensitive) primary melanoma cultures. RNA gel shift assays demonstrated protein(s) binding to the 3'-UTR of TRAIL-R2 mRNA that were more evident in TRAIL-resistant cultures with low TRAIL-R2 protein expression. A 23-base fragment of the 3'-UTR inhibited binding of the proteins to the 3'-UTR, and a probe using this fragment bound to proteins in TRAIL-selected melanoma lines and early passage isolates of melanoma. Binding of the 3'-UTR probe to the cytosolic protein(s) was induced by exposure to TRAIL and was lost from the TRAIL selected lines 2-3 days after withdrawal of TRAIL from the cultures. These results are consistent with post-transcriptional regulation of TRAIL-R2 expression by cytosolic proteins induced by TRAIL that bind to the 3'-UTR region of TRAIL-R2 mRNA.

Privatisation — A History and Survey of Changes in Organisation Structures, Cultural and Environmental Profiles

This paper provides a brief history of changes after privatisation to organisational structures and cultural profiles of affected entities. It assesses the experience of change in the electricity industry in New Zealand, the Commonwealth Serum Laboratories and the State Electricity Commission of Victoria and then examines results of a survey of senior executives of organisations privatised in Australia between 1990 and 1998. These senior executives had access to knowledge of pre‐ and post‐privatisation conditions and their answers to a series of questions on organisational structure, cultural and environmental issues were analysed. The detailed answers involve limited areas of ‘no change’ but, critically, significant cultural changes relating to private ownership are established. These are summarised for readers' convenience by tables and discussed within the text.

Tiger-snake antivenom for suspected small-eyed snake envenomation

Despite its relative frequency and widespread distribution throughout eastern Australia, bites by the nocturnal eastern small-eyed snake, Cryptophis nigrescens, have seldom been recorded. There is no standard laboratory test or proven antidote for its venom, which is capable of causing life-threatening myolysis in humans. A 39-year-old man presenting to hospital with acute abdominal and limb muscle pains, was noted to have a pair of puncture wounds on his leg. No venom was detected in the urine with the Commonwealth Serum Laboratories’ Venom Detection Kit. The only blood abnormality was a grossly elevated creatine kinase at 48 000 IU/L. A presumptive diagnosis of Cryptophis nigrescens envenomation was made and the patient treated with tiger-snake antivenom (3000 U). Creatine kinase levels started to fall almost immediately and the patient made a full recovery. We believe this is the first time tiger-snake antivenom has been used specifically for suspected Cryptophis nigrescens envenomation.