THE RESEARCH ENTERPRISE – 90TH ANNIVERSARY Jewels in the crown: The Medical Journal of Australia’s 10 most-cited articles Ann T Gregory According to data from the Institute for Scientific Information (ISI), the most-cited MJA article is Cade’s ground-breaking report on the effect of lithium in mania (1949; 888 citations), followed by Marshall et al’s reports on the role of Helicobacter pylori in gastroduodenal disease (1985; 766 and 523 citations, respectively). Others in the “top 10” span decades and disciplines; all have a common grounding in Australian data of global relevance. (MJA 2004; 181: 9-12) or the year 1995, shortly after the 80th anniversary of The 1The MJA’s top 10 articles, by citation analysis Medical JournalThe Medicalof Australia Journal (MJA of ),Australia researchers from the Australian National University used citation analysis to deter- Number 1 (888 citations) F ISSN: 0025-729X 5 July 2004 Cade JFJ. Lithium salts in the treatment of psychotic excitement. mine Australia’s contribution to new knowledge in medical and 181 1 9-12 Med J Aust 1949; 2: 349-352. health©The sciences. Medical They Journalfound that of AustraliansAustralia 2004 contributed 2.5% of all publicationswww.mja.com.au in the Science Citation Index — 18 390 publica- Number 2 (766 citations) tions, Thewhich Research had been Enterprise cited over – 90th 88 000Anniversary times.1,2 In 2003, the MJA Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ. used citation data provided by Thomson ISI (www.isinet.com) to Attempt to fulfil Koch’s postulates for pyloric campylobacter. identify the “top 10” articles published in the MJA — that is, the Med J Aust 1985; 142: 436-439. articles which had been cited most often. Data comprised citations Number 3 (523 citations) within journal articles covered by the database of the Institute for Marshall BJ, McGechie DB, Rogers PA, Glancy RJ. Scientific Information (ISI) for the years 1945–2002; thus, articles Pyloric campylobacter infection and gastroduodenal disease. published before 1945 could be cited. Med J Aust 1985; 142: 439-444. The MJA top 10 articles span more than 60 years (Box 1). They Number 4 (299 citations) have in common a grounding in Australian data, but a global Derrick EH. “Q” fever, a new fever entity: clinical features, diagnosis relevance. In addition, all provide evidence of the importance of and laboratory investigation. Med J Aust 1937; 2: 281-299. basic as well as clinical research, and of that endangered species Number 5 (267 citations) the physician–scientist. Swan C, Tostevin AL, Moore B, Mayo H, Barham Black GH. Congenital defects in infants following infectious diseases during pregnancy. Med J Aust 1943; 2: 201-210. Simple cation holds promise as psychotropic agent Number 6 (203 citations) John Cade (1912–1980), the author of our most-cited article, once George LL, Borody TJ, Andrews P, Devine M, Moore-Jones D, described himself self-deprecatingly as “an unknown psychiatrist, Walton M, Brandl S. Cure of duodenal ulcer after eradication of working alone in a small chronic [sic] hospital with no research Helicobacter pylori. Med J Aust 1990; 153: 145-149. 3 training, primitive techniques and negligible equipment”. Number 7 (170 citations) Born in Murtoa, a small country town in Victoria, Cade seemed Trautner EM, Morris R, Noack CH, Gershon S. destined to enter psychiatry. His father was a psychiatrist, and as a The excretion and retention of ingested lithium and its effect on the child Cade lived in the grounds of various “lunatic asylums”. He ionic balance of man. Med J Aust 1955; 2: 280-291. entered psychiatry in 1936, shortly after graduating in medicine Number 8 (169 citations) (with honours in all subjects), but spent much of the Second Bower C, Stanley FJ. Dietary folate as a risk factor for neural-tube World War as a prisoner of war in Changi, Singapore, returning to defects: evidence from a case–control study in Western Australia. Australia as a 40 kg “walking skeleton”.4,5 Med J Aust 1989; 150: 613-619. Cade’s interests included all the sciences, and his “enquiring Number 9 (167 citations) mind” stayed with him throughout life. The coauthor of his first Wilson RMcL, Runciman WB, Gibberd RW, Harrison BT, article (published in 1940), detailing the serological response to Newby L, Hamilton JD. The Quality in Australian Health Care Study. influenza virus infection, was none other than Frank Macfarlane Med J Aust 1995; 163: 458-471. 6 Burnet. Number 10 (166 citations) While Cade was investigating potential anticonvulsant agents in Borody TJ, Cole P, Noonan S, Morgan A, Lenne J, Hyland L, Brandl guinea-pigs, he came to suspect that the cation lithium had a S, Borody EG, George LL. Recurrence of duodenal ulcer and sedative effect which might be useful in treating mania. He Campylobacter pylori infection after eradication. Med J Aust 1989; demonstrated this sedative effect in guinea-pigs, and then took 151: 431-435. lithium himself, before extending his study to patients.3 In his MJA article, Cade reported the results of a study of the effect of lithium salts in 10 patients with mania (as well as six with schizophrenia The Medical Journal of Australia, Sydney, NSW. and three with “melancholia”). Lithium had a clear effect in mania. Ann T Gregory, MB BS, GradDipPopHealth, Deputy Editor. He published no further research on lithium, but did search for Reprints will not be available from the author. Correspondence: other cations with psychotropic activity.3 In commenting on his Dr Ann T Gregory, The Medical Journal of Australia, Locked Bag 3030, research career, he said: “My own research efforts have been Strawberry Hills, NSW 2012. [email protected] MJA • Volume 181 Number 1 • 5 July 2004 9 THE RESEARCH ENTERPRISE – 90TH ANNIVERSARY sporadic over many years. Most have ended 2 Illustrations from Marshall et al’s pylori to epidemic gastritis with hypo- in blind alleys. Some have been successful. two “top 10” MJA articles chlorhydria. All have been fun. In the process I have In the second MJA article, Marshall and learned a greater deal . , and en passant colleagues proposed that pyloric campylo- something of the causes and effective treat- bacter infection was responsible for damage ment of manic–depressive illness.”7 to the duodenal epithelium, as well as the Cade’s findings were not immediately gastric antral mucosa, based on gastroduo- accepted in the rest of the world (and not denal biopsy and culture findings from over until the 1970s in the United States), so it is 100 patients referred to their dyspepsia not surprising that further notable research research clinic (Box 2B). on lithium was also conducted in Australia. Looking back on these discoveries, Mar- Ranked seventh in the MJA top 10, The shall later wrote that early reports of an excretion and retention of ingested lithium and association between peptic ulcer and H. its effect on the ionic balance of man was A. Numerous Helicobacter pylori organisms pylori were met with extreme scepticism by published in 1955. The authors included in a gastric biopsy specimen from Barry many doctors, who were convinced that Trautner, a physiologist at the University of Marshall, taken 10 days after he ingested a psychic stress, cigarette smoking and hyper- Melbourne, and Noack, a psychiatrist at pure culture of the organism (Warthin–Starry acidity were the causes of peptic ulcer. Melbourne’s Mont Park Hospital. Their silver stain; original magnification x 900). Reports of the first therapy ever shown to research, conducted on themselves and on heal gastritis received “a cool reception at patients with mania, showed that lithium is gastroenterological meetings”.10 retained during the acute phase of mania, Compared with Cade’s era, communica- necessitating higher doses. These can be tion among the world’s scientific community reduced as the mania resolves. They also had accelerated greatly, and, in 1991, the showed that intercurrent illness increases first convincing study of cure of duodenal the risk of lithium toxicity. ulcer through eradication of H. pylori was published in the United States. However, this was preceded by another pair of notable Spiral bacterium linked with gastritis articles on the same topic in the MJA, from and peptic ulcer the Centre for Digestive Diseases in Sydney. Today, we know that Helicobacter pylori colo- In 1989, the study by Borody and col- nises the stomach and infects about half the leagues, which ranks tenth in the MJA top world’s population.8 Further, it has infected 10, showed that “triple chemotherapy” with people since the dawn of human history, and bismuth, tetracyline and metronidazole its geographic variation is being used to map could lead to long-term eradication of H. the earliest human migrations, including the pylori in most patients with duodenal ulcer arrival of Europe’s first neolithic farmers.9 or non-ulcer dyspepsia. Further, they sug- However, as recently as two decades ago, gested that this eradication could reduce notwithstanding reports suggesting other- recurrence of, or even cure, duodenal ulcer. wise (“dispersed over 100 years, in journals B. Heavy growth of H. pylori from an antral The group subsequently reported such cure of different languages and subspeciali- biopsy specimen from a patient with in their 1990 MJA article, which ranks sixth ties”10), the prevailing dogma was that the duodenal ulcer. (Larger white colonies are in the top 10. commensal flora of the mouth.) human stomach was sterile, and that bac- H. pylori infection is now recognised as teria could not survive in gastric acid.10 the major cause of peptic ulcer disease and Gastroenterologist Barry Marshall and an important risk factor for gastric malig- pathologist Robin Warren first described the association of a nancy.