EMIGRANT ETHERIST: THE MEDICAL AND SCIENTIFIC INFLUENCE OF JOHN HENRY HILL LEWELLIN (1818–86), PIONEER ANAESTHETIST AND SURGEON AND PATRON OF BOTANY IN AUSTRALIA

The pioneer anaesthetists in Australia came from varying professional backgrounds. To the influence of Belisario in Sydney, Pugh in Launceston and Buchanan in Stroud, can be added the role of John Henry Hill Lewellin (1818–86). Lewellin immigrated from Scotland to become a pioneer Melbourne etherist and surgeon from 1852. Born in India, he studied surgery at Bart's Hospital in London (1842) and as a Member of the Royal College of Surgeons from that year, practised as a surgeon and dentist in Glasgow. On 19 December 1846 he was the first to use the newly discovered ether in anaesthetic practice in Glasgow, and one of the first to do so in the United Kingdom. He emigrated to Melbourne in 1852, where he achieved considerable success in the management of tetanus with ether. He was an active member of the Medical Society of Victoria and a vigorous participant in its clinical discussions. As a surgeon, Lewellin pursued a significant community role in the broader Melbourne society of the day. He served as a Magistrate, became Vaccination Officer in Victoria and, as an active doctor-soldier, served with sequential promotions finally to the rank of Surgeon-Major in the Volunteer Force (Rifles) of the Colony. He became a patron of science and a supporter of the Melbourne botanist, Ferdinand von Mueller. Of all his prodigious scientific writing, von Mueller dedicated Volume 8 of his Fragmenta to his surgical colleague, as one 'who is a most skilful physician' and later as 'a most generous promoter of my investigations'. Lewellin's legacy, in his pioneering contributions as an early anaesthetist in two continents, lives on in the scientific names of two floral species which perpetuate his name.     

Muscle insulin-like growth factor status, body composition, and functional capacity in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients typically have reduced muscle mass and diminished functional capacity. The role of the muscle insulin-like growth factors (IGFs), a principal anabolic system that is involved in protein synthesis and that has downregulation that is implicated in muscle loss in animal models of uremia, has previously not been assessed in vivo in HD patients. METHODS: Seventeen HD patients were compared cross-sectionally with 17 age-, sex-, and body mass index-matched healthy controls. Body composition was assessed by dual energy x-ray absorptiometry and bioelectrical impedance spectrometry; functional capacity by hand grip strength, quadriceps strength, and 30-second sit-to-stand test; systemic inflammation by tumor necrosis factor-alpha (TNF-alpha) and TNF receptor 1 (TNFR1); serum and muscle IGF-I and IGFBP-3 by radioimmunoassay; and fragmentation of serum IGFBP-3 by Western immunoblotting. RESULTS: Appendicular lean mass was significantly decreased in HD patients compared with controls (17.6 +/- 0.9 versus 21.5 +/- 1.5 kg, P < .05), as were all measures of functional capacity (P < .01 to .001), and highly significant positive correlations between appendicular lean mass and functional capacity were evident (appendicular lean mass and hand-grip strength, quadriceps strength, 30-second sit-to-stand test, all P < .001). TNF-alpha and TNFR1 were elevated in patients (P < .001). Although serum IGF-I and IGFBP-3 levels did not differ between the groups (P = .295 and .379 respectively), fragmented IGFBP-3 levels were increased (53.1 +/- 16.0 versus 29.81 +/- 15.3%, P < .005). In contrast, muscle IGF-I was substantially diminished in the patient group (n = 7) relative to control (n = 5) levels (0.84 +/- 0.06 versus 2.78 +/- 1.80 pg/microg, P < .05). CONCLUSIONS: We provide evidence of reduced IGF-I in HD patients' skeletal muscle that may be a causal factor in the muscle wasting characteristic of this population. Future research should determine the exact consequences and causes of alterations to the muscle IGF system in HD patients.     

Challenges for nephrology nurses in the management of children with chronic kidney disease.

An important treatment goal for pediatric nephrology caregivers is the optimization of a child's capacity for normal growth and development. However, the physiologic and metabolic derangements associated with chronic kidney disease (CKD) significantly alter these processes, creating important challenges in the care of affected children. Evidence-based clinical practice guidelines support early recognition and treatment of CKD-related complications to improve growth and development and, ultimately, quality of life for children with this chronic condition.     

CAG repeat number governs the development rate of pathology in Huntington's disease

We compared the number of CAG repeats, the age at death, and the severity of neuropathology in 89 Huntington's disease brains. We found a linear correlation between the CAG repeat number and the quotient of the degree of atrophy in the striatum (the brain region most severely affected in Huntington's disease) divided by age at death, with an intercept at 35.5 repeats. The largest CAG repeat length, therefore, at which no pathology is expected to develop is 35.5. These results imply that striatal damage in Huntington's disease is almost entirely a lineaar function of the length of the polyglutamine stretch beyond 35.5 glutamines multiplied by the age of the patient. Thus, it is predicted that the pathological process develops linearly from birth. Analysis of other measures of striatal function could test this hypothesis and might determine when treatment for CAG repeat diseases should start.     

Functional properties of recombinant GABAA receptors composed of single or multiple β subunit subtypes

GABA_A receptor (GABAR) isoforms in the central nervous system are composed of combinations of α(1–6), β(1–4), γ(1–4), δ(1) and (1) subunit subtypes arranged in a pentamer. Many regions of the brain express high levels of mRNA encoding several different subunits and even multiple subunit subtypes. The stoichiometry of GABAR isoforms is unclear, and the number and identity of individual subunit subtypes that are coassembled remain uncertain. To examine the role of β subunit subtypes in the functional properties of GABARS and to determine whether multiple β subtypes can be coassembled in functional GABARs, plasmids containing cDNAs encoding rat β1 and/or β3, α5 and γ2L subtypes were cotransfected into L929 fibroblasts. The properties of the expressed receptor populations were determined using whole-cell and single-channel recording techniques. The α5β1γ2L isoform was less sensitive to GABA than the α5β3γ2L isoform. α5β1γ2L isoform currents were also insensitive to the allosteric modulator loreclezole, while α5β3γ2L isoform currents were strongly potentiated by loreclezole. Fibroblasts transfected with plasmids containing cDNAs for both β1 and β3 subtypes along with α5 and γ2L subtypes produced a receptor population with an intermediate sensitivity to GABA which was insensitive to loreclezole. These results suggest that functional GABARs can be formed that contain two different β subunit subtypes with properties different from receptors that contain only a single β subtype and that the β subunit subtypes influence the response of GABARs to GABA and to the allosteric modulator loreclezole.