CT pulmonary angiography: optimising acute thoracic imaging by fixed-timing contrast medium delivery with a modified breathing instruction.

AIM: To compare the thoracic vascular opacification achieved using the standard bolus-tracking protocol (BTP) with a fixed-timing protocol (FTP) with a modified breathing instruction during computed tomography pulmonary angiography (CTPA) examinations. MATERIALS AND METHODS: A single-centre review of CTPA examinations performed between July 2018 and January 2019 using the BTP or FTP and weight-based contrast dosing of 20 mg iodine/kg body weight/s for 20 seconds at 100 kV tube potential. Radiodensity (in Hounsfield units) was analysed in the right ventricle, main pulmonary artery (MPA), left atrium, left ventricle, and ascending and descending thoracic aorta (DTA). A p-value of <0.05 was considered significant. RESULTS: Of 782 examinations, 88 BTP and 90 FTP examinations were included. Mean attenuation of the MPA was similar in the FTP (396 ± 106 HU) and BTP (362 ± 119 HU; p=0.06); however, good-quality (≥250 HU) MPA opacification was achieved in more FTP examinations (87/90, 96.7%) compared to the BTP (73/88, 82.9%; p=0.002). Mean attenuation of the DTA was better in the FTP (325 ± 72 HU) than the BTP (228 ± 75 HU; p <0.0001), with good-quality opacification (≥250 HU) in 76/90 (84.4%) FTP examinations compared with 36/88 (40.9%) BTP examinations (p <0.001). CONCLUSION: The FTP achieves better opacification of the MPA and DTA compared to the BTP.

A quality-improvement project to enhance systemic arterial contrast opacification in CT for trans-catheter aortic valve implantation.

AIM: To assess improvement in arterial opacification by optimising the contrast medium dosing protocol for computed tomography (CT) prior to trans-catheter aortic valve implantation (TAVI). MATERIALS AND METHODS: A wide variation in arterial opacification was observed in the initial CT TAVI protocol (standard protocol). The practice was optimised by considering the time required for the examination and optimising contrast medium flux. This became the optimised protocol with a 30-second contrast medium bolus of iodine flux 15-19 mg iodine/kg body weight/second (mg/kg/s). Attenuation (mean HU) in (a) the ascending aorta (gated systolic acquisition) and (b) the ascending, descending thoracic (at carina), infra-renal abdominal aorta, and right common iliac artery (non-gated acquisition) was measured. Thirty-one sequential optimised examinations were compared to 31 prior standard protocol examinations. RESULTS: There was no difference between the standard and optimised groups regarding age, sex, weight, body mass index (BMI), or voltage. The mean bolus durations were 24.9±4.4 seconds for the standard and 30±0.3 seconds for the optimised protocols (p<0.001). Although there was no difference in the attenuation in the gated ascending aorta (p>0.99), there was improvement at all other anatomical points in the non-gated examinations of the optimised protocol (p<0.002). CONCLUSION: Optimising contrast medium flux and matching bolus duration to the CT technology dramatically improves the vascular access component of TAVI planning and provides a reliable method to achieve objectively enhanced arterial opacification. This work highlights how to obtain good arterial contrast medium opacification in haemodynamically fragile patients without excessive contrast medium volumes.

Transvaginal rectopexy using the Flex® Colorectal Drive Robotic System: a proof-of-concept approach to rectal prolapse.

BACKGROUND: The aim of this study was to demonstrate a proof-of-concept approach to rectopexy that would provide the durability of the transabdominal procedure through use of sacral rectopexy with the decreased morbidity of a perineal procedure. This was done by utilizing a transvaginal approach and developing the rectovaginal space to accommodate sacral rectopexy placement using the Flex® Colorectal Drive Robotic System by Medrobotics (Medrobotics Corp., Raynham, MA, USA). METHODS: A fresh female cadaver was acquired and placed in the high lithotomy position. The rectovaginal space was developed to accommodate the trocar of the Flex robot using blunt and sharp dissection between the posterior vaginal wall and anterior rectum. A piece of mesh was introduced into the space and using an endoscopic tacker, which was secured to the sacral promontory. The mesh was secured to the anterior rectal wall using interrupted vicryl sutures. The purse string suture was removed and the rectovaginal orifice was closed using a running vicryl suture. At the completion of the procedure, a low midline laparotomy was conducted to verify anchoring of the mesh appropriately at the sacral promontory. RESULTS: This proof-of-concept protocol is the first description of the Flex® Colorectal Drive being used successfully to perform a transvaginal rectopexy for rectal prolapse in a cadaver. This is also the first description of the Flex® Colorectal Drive robot being used transvaginally. CONCLUSIONS: This proof-of-concept approach demonstrates that transvaginal rectopexy using the Flex® Colorectal Drive is a potential surgical option to address rectal prolapse that could provide patients the durability of a transabdominal approach with the decreased morbidity of a perineal approach. While early results are promising, additional cadaveric studies are required before this procedure can be attempted in vivo.

St John's Hospital (Morton House), Launceston, Australia: A history of the hospital and Dr William Russ Pugh's first operations under ether.

On 7 June 1847, William Russ Pugh, MD, performed two operations at the St John's Hospital and Self-Supporting Dispensary, Launceston, Tasmania, while his patients were rendered insensible by the inhalation of sulphuric ether. These operations are the earliest documented surgical operations under ether in Australia. St John's Hospital officially opened on 1 September 1845. The hospital may have closed in late 1853 because of financial difficulties. The two-storey Georgian-style building which served as the hospital was completed c1831-1832. It has served as a residence, school, boarding school, hospital, medical consulting rooms and commercial offices. The building is now known as Morton House. We could not identify the date when the name Morton House was adopted, or explain the origin of the name. The earliest identified use of this name is in May 1873 in a newspaper advertisement for boarders. No person with the surname Morton is known to have been associated with the building as an owner or as a tenant. The name Morton House may honour William T.G. Morton, MD, the Boston dentist who performed the first public demonstration of surgical etherisation on 16 October 1846.

Temporal and Spatial Development of Cercospora Leaf Spot of Faba Bean Influenced by In Situ Inoculum.

The temporal and spatial dynamics of Cercospora leaf spot on susceptible and resistant lines of faba bean grown in or at defined distances from soil with residues infested by Cercospora zonata were examined in South Australia in 2005 and 2006. The disease was first observed on susceptible seedlings 49 days after sowing (DAS) in soil that had been sown with faba bean every 3 years since 1997 (positive soil zone for C. zonata) but was delayed by 1 week in adjacent soil (0 to 16 m away) with no history of cultivation of faba bean (negative soil zone). The incidence of diseased seedlings from 49 to 63 DAS showed a gradient from 4 to 16 m from the infested soil and was significantly greater for susceptible plants grown in the positive versus negative soil zones in field trials conducted in 2005 and 2006 (92 versus 30% in 2005, χ21 = 32.2, P < 0.001; 98 versus 55% in 2006, χ21 = 12.1, P < 0.001). The incidence of Cercospora leaf spot on the resistant line 1322/2 was significantly less (χ26 = 171.7; P < 0.001) than on the susceptible line 'Farah' at that time in both years, with fewer than 5% of the seedlings showing the disease. However, a gradient was shown at 70 to 84 DAS, where disease incidence was significantly greater on line 1322/2 in the positive soil zone than on plants in the negative soil zone in both years (62 and 18%, respectively, with χ21 = 27.9, P < 0.001 in the 2005 trial; and 47 and 6%, respectively, with χ21 = 33.3, P < 0.001 in the 2006 trial). At peak disease severity on Farah, Cercospora leaf spot mean leaf area diseased (%LAD) was severe (85 ± 4.3%) on leaves of the three nodes closest to the soil surface, and much less severe (1 ± 0.6%) in the upper canopy. Defoliation combined with %LAD was used to describe the loss of photosynthetic leaf area (%LPLA) in both cultivars, on both soil zones, in each year. Nonlinear regression analyses using a logistic model described disease development over time on susceptible plants grown in infested soil (e.g., for +12-m blocks within infested soil, y = 2.66 + 46.08/[1 + exp(-0.23 × [X - 40.92])] in 2005 and y = 0.49 + 5.02/[1 + exp(-0.14 × [X - 28.30])] in 2006, where X = DAS and y = %LPLA, with both regressions significant at P < 0.001), whereas an exponential model (e.g., for -12-m blocks from infested soil, y = 0.23 + 0.77 × 1.04X in 2005 and y = 0.44 + 0.56 × 1.04X in 2006, both at P < 0.001) best described disease gradients with increasing distance from the inoculum source. Paired t tests of %LPLA at 77 and 98 DAS showed significant differences in disease severity in the positive versus negative soil zones and a steep gradient in %LPLA from 0 to 4 m from the inoculum source. The role of infested faba bean residue in survival of C. zonata over time was also examined using a pot-bioassay and in situ field assay. When residues were removed from the soil surface or depleted rapidly by animal grazing, the amount of C. zonata inoculum in the soil was significantly less (P < 0.001) than for soil with residue remaining on the soil surface. C. zonata survived in soil and remained infective for at least 30 months after harvest of an infected faba bean crop.

Dr Pugh and the myth of the illicit still.

In her valuable history of the arrival of the news of etherisation in Australia and its implementation by many doctors and dentists, titled One Grand Chain, the late Dr Gwen Wilson asserted that the dentist and the doctor who pioneered etherisation in Australia, "Belisario and Pugh, …were charged by the authorities with possession of an illicit still." This paper examines the evidence for the truth or otherwise of this assertion, in relation to Dr Pugh.

The role of Dr Isaac Aaron and the Australian Medical Journal in the dissemination of information about etherisation in the 1840s.

Isaac Aaron (1804 to 1877), an ambitious young medical practitioner, arrived in Sydney from Britain in 1838 and was registered by the New South Wales Medical Board the following year. After contributing to the Australian Medical Journal, established in August 1846 by William Baker, he became the editor in December and acquired it in May the following year. Dr Pugh became the most prolific local contributor to the journal but he and the editor had a somewhat 'prickly' relationship. Aaron was very critical of etherisation when the first news arrived in Australia, but Pugh chose Aaron's journal in which to report his initial and subsequent experience with the technique. Aaron repeatedly appealed for experimental evidence and rational decision-making to determine the place of etherisation in medical practice. Unfortunately for Australian medicine, Aaron had to suspend the publication of the journal in October 1847, lacking both time and the support of the profession necessary to maintain it. This created an unanticipated adverse outcome for Dr Pugh.

Dr Pugh: a poisoner?

On 16 February 1845 the Reverend W. H. Browne, rector of St John's Church in Launceston, Van Diemen's Land, wrote in his journal, "My dear Wife died very suddenly almost immediately after and in consequence of taking a preparation of Hyd. Cyan. Acid prepared & supplied by Dr Pugh". This journal entry raises a number of questions. Was Dr Pugh treating a condition which he thought merited that treatment or was it a ghastly mistake? Was Caroline Browne suffering from pulmonary tuberculosis? Was hydrocyanic acid an accepted treatment at that time? Did Mrs Browne take the wrong dose? Was an incorrect concentration of the drug prepared by Dr Pugh? Did he use the wrong pharmacopoeia in preparing the hydrocyanic acid? Why was there no inquest? Only some of these questions can be answered.

William Russ Pugh's remarkable life: natural scientist, innovative anaesthetist and founding member of the Royal Society of Tasmania.

While well known in anaesthetic circles for being the first to provide ether anaesthesia for a surgical procedure in June 1847 in Launceston, Tasmania, William Russ Pugh's achievements in the field of natural history are less well known. He personally assisted Count Peter de Strzelecki in the chemical analysis of Australian coal and mineral samples and provided the laboratory space and equipment. His analytic skills were utilised by coroners in cases of poisoning. He was consulted about a ship's cargo which threatened to spontaneously combust in Launceston's port. He was a founding member of the Tasmanian Society and subsequently of the Royal Society of Tasmania. He made many presentations on geology, zoology, botany, mineralogy and meteorology to meetings of both Societies. These scientific interests may have provided the knowledge and motivation which encouraged Pugh to proceed so confidently with the introduction of ether anaesthesia.

Gilles vs Pugh and the lost letter.

In June 1842 the wife of Lewis W Gilles, a banker in Launceston, wrote to Mrs Pugh, inviting her and her husband, Mr William Russ Pugh, to an entertainment and ball. The Pughs neither responded to the invitation, nor attended the ball. Mrs Gilles mentioned the discourtesy of their non-attendance to a friend, who the following morning brought the complaint to the attention of Dr Pugh. Pugh immediately wrote a brief note explaining that neither he nor his wife had received the invitation. Further correspondence between Gilles and Pugh ensued, becoming more and more bitter until Pugh publicly insulted Gilles. The Launceston Club, of which both men were members, ultimately became a casualty of the dispute and was dissolved. A Supreme Court defamation and libel case followed with Gilles as plaintiff and Pugh as defendant. Gilles won the case but received only token damages. And the missing letter? Too late, Mrs Pugh's maid found it tucked between the pages of a periodical on the dresser

The perils of pointing the finger: a lesson for Dr. Haygarth.

Mr. William Russ Pugh, well known for his anaesthetic activities, and probably the first in Australia to administer ether anaesthesia for a surgical operation in May 1847, was involved in several court cases in Launceston, Tasmania in 1842 and 1843. At that time Tasmania was known as Van Diemen's Land. Two of the most dramatic cases ensued after a young doctor, Dr. Burton George Haygarth, a recent arrival in the colony of Van Diemen's Land, was persuaded to accuse Pugh of manslaughter. Because of Pugh's standing in Launceston the cases attracted enormous public attention and support for Pugh. The outcome for Dr. Haygarth was very unpleasant and not something which he had anticipated.

An experimental comparison of Pycnogenol and methylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD).

Twenty-four adults (24 to 53 years old) with Attention-Deficit/Hyperactivity Disorder (ADHD), Combined Type, were studied in a double-blind, placebo-controlled, crossover study of Pycnogenol and methylphenidate. Pycnogenol is an antioxidant derived from the bark of the French maritime pine tree. Methylphenidate is a standard pharmaceutical intervention for ADHD. Anecdotal reports suggest that Pycnogenol improves concentration in adults with ADHD without adverse side effects. Participants received Pycnogenol, methylphenidate, and placebo, each for three weeks, in a randomized and counterbalanced order. Although ADHD symptoms improved during treatment, neither methylphenidate nor Pycnogenol outperformed the placebo control, as measured by self-report rating scales, rating scales completed by the individual's significant other, and a computerized continuous performance test. The conservative dosage levels and relatively brief length of treatment may have contributed to the absence of significant differences among treatment conditions. Implications for future research are noted.

Persistent cardiovascular effects of chronic renin-angiotensin system inhibition following withdrawal in adult spontaneously hypertensive rats.

OBJECTIVES: It is generally accepted that short-term (4 weeks) inhibition of the renin-angiotensin system (RAS) of young spontaneously hypertensive rats (SHR) in their prehypertensive phase confers long-lasting protection from fully hypertensive levels in adulthood. However, there is very little data pertaining to the effects of such treatment in adult SHR with established hypertension. Therefore, we determined the relative effects of angiotensin converting enzyme (ACE) inhibition (perindopril), AT1 receptor blockade (candesartan cilexetil) and RAS-independent vasodilatation (hydralazine) and their withdrawal in adult SHR, on blood pressure measured by radiotelemetry, as well as on cardiac and vascular structure. METHODS: Adult male SHR were instrumented with radiotelemetry probes to measure blood pressure and heart rate continuously. SHR were given either vehicle, perindopril (1 mg/kg per day), candesartan cilexetil (2 mg/ kg per day) or hydralazine (30 mg/kg per day) at equieffective depressor doses for 4 weeks (treatment study). Separate groups of animals were also given identical treatments but were then monitored for a further 8 weeks after drug withdrawal (withdrawal study). An indirect in-vivo assessment of whole body vascular hypertrophy (mean arterial pressure during maximum vasoconstriction) was made during and after drug withdrawal, as was the pressor activity evoked by angiotensin I and angiotensin II. The effect of antihypertensive treatment on microalbuminuria was also assessed during and after drug withdrawal. Finally, left ventricular: body weight (Iv: bw) and mesenteric media: lumen ratios were determined either immediately after 4-week treatment (treatment study) or 8 weeks later (withdrawal study). RESULTS: Perindopril persistently lowered blood pressure in adult SHR whereas blood pressure returned to vehicle levels within approximately 4 and 15 days after withdrawal of hydralazine and candesartan cilexetil, respectively. Cardiac hypertrophy was reduced by all three treatments, but to a lesser extent by hydralazine (treatment study), and this regression of cardiac hypertrophy persisted only with both types of RAS inhibition (withdrawal study). Vascular hypertrophy, measured indirectly and directly, was also reduced by all three treatments, with perindopril and candesartan cilexetil causing hypotrophic and eutrophic remodelling, respectively (treatment study), although these changes were generally not maintained after drug withdrawal (withdrawal study). Angiotensin I-induced pressor responses were equally inhibited during treatment with either candesaran cilexetil or perindopril (and were unaffected by hydralazine) but normalized rapidly in both groups (within approximately 2-4 days) after withdrawal of RAS inhibition. In addition, there was a small age-related increase in microalbuminuria over the study period, which was not significantly affected by any treatment. CONCLUSIONS: Following 4-week treatment, candesartan cilexetil, perindopril and hydralazine caused similar antihypertensive effects; however, only perindopril persistently reduced blood pressure following drug withdrawal. Both types of RAS inhibition and hydralazine caused marked cardiac and vascular remodelling during treatment, whereas only the RAS inhibitors persistently regressed cardiac hypertrophy 8 weeks later. Collectively, these results indicate the importance of the RAS for the maintenance of hypertension and cardiovascular hypertrophy in adult SHR, as well as identifying differential effects of ACE inhibition and AT1 receptor blockade on persistent blood pressure reduction.

Restraint stress : differential cardiovascular responses in Wistar-Kyoto and spontaneously hypertensive rats.

With the use of a restraint stress paradigm, both normotensive Wistar-Kyoto (WKY ) rats and spontaneously hypertensive rats (SHR) underwent acute (1-hour restraint in a Perspex tube), chronic (1-hour restraint for 10 consecutive days), or no-restraint (control) stress. Rats experiencing chronic restraint were previously implanted with telemetric probes to measure heart rate and blood pressure. Basal (prestress session) cardiovascular variables did not change during the course of the study (SHR: mean arterial pressure 129+/-1 mm Hg, heart rate 288+/-4 bpm; WKY rats: mean arterial pressure 103+/-1 mm Hg, heart rate 285+/-3 bpm). Restraint caused tachycardia and pressor responses in the WKY rats and SHR, but these effects were greater in the hypertensive strain. The duration of restraint-induced tachycardia did not change in the WKY rats between acute and chronic stress; however, a graded reduction in the duration of restraint-induced tachycardia occurred in the SHR, decreasing to WKY rat levels by day 7 of the 10-day regimen. These data indicate that although the WKY rats can effectively "cope" within a single period of restraint, the coping mechanism is apparently impaired in the SHR compared with the WKY rats. A reduced capacity to cope with processive stressors may thus have an affect on cardiovascular regulation and represent an additional risk factor in hypertension.

Genetic diversity in Australian wheat varieties and breeding material based on RFLP data.

Restriction fragment length polymorphisms (RFLPs) have been used to characterise the genetic diversity of wheat (Triticum aestivum) germplasm. One hundred and twenty-four accessions comprising all major Australian wheat varieties and lines important for breeding purposes were assayed for RFLPs with clones of known genetic location and selected to give uniform genome coverage. The objectives of this study were to determine RFLP-based genetic similarity between accessions and to derive associations between agronomically significant traits and RFLP phenotypes. Ninety-eight probes screened against genomic DNA digested with five restriction endonucleases detected a total of 1968 polymorphic fragments. Genetic similarity (GS) calculated from the RFLP data ranged from 0.004 to 0.409 between accessions, with a mean of 0.18. Cluster analysis based on GS estimates produced four groupings that were generally consistent with available pedigree information. Comparisons of the RFLP phenotypes of accessions containing disease resistance genes present on introgressed alien segments enabled the identification of specific alleles characteristic of these regions. Associations were derived for a range of stem-rust, leaf-rust and yellow-rust resistance genes. These results suggest that RFLP analysis can be used for the characterisation and grouping of elite breeding material of wheat and RFLP profiling can identify chromosome segments associated with agronomic traits.