The use of real-time digital video in the assessment of post-operative outcomes of breast reconstruction.

INTRODUCTION: Outcome measures of breast reconstruction have used panel assessment of photographs. This provides limited information to the assessor as these images are static.. The aim of this study was to assess whether the use of digital video was a valid assessment tool and to compare its use against photography. METHODS: 35 patients post-reconstruction underwent photography, digital video capture and completed Breast Cancer Treatment Outcomes Scale (BCTOS) questionnaires. The photographs/video clips were randomised and shown to a 21 member panel. Opinions on aesthetic aspects of the reconstruction were assessed using the BCTOS and Harris scale. Panel inter-rater agreement and patient-panel correlation was assessed using Kendall's Coefficient of Concordance and Spearman's rank correlation tests respectively. RESULTS: There was a "moderate" degree of inter-rater agreement amongst panel members in all categories. Greater agreement occurred using video footage to assess overall cosmesis (0.548 vs 0.507) and shape (0.505 vs 0.486). Video showed a greater degree of correlation with patient self-assessment scores in comparison to photography (0.311 vs 0.281). CONCLUSION: Video footage coupled with panel assessment is a valid method of assessing post-operative outcomes of breast reconstruction and appears superior to still photographs in terms of inter-rater agreement and correlation with patient self-assessment.

Bilateral deep inferior epigastric perforator flaps based on unilateral perforators.

This report highlights the case of an unusual bilateral breast reconstruction using bilateral Deep Inferior Epigastric Perforator flaps based solely upon unilateral perforators. The usual lower paramedian perforating vessels were absent on one side and subsequently the main abdominal flap was split obliquely (rather than midline) to base both individual flaps on perforators arising from the same side. The operation was a success with no flap complications post-operatively.

Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent.

Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), a significant number of patients have anti-nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti-nuclear antibodies as well as suggestive evidence that antibodies to gp210 predict a poor outcome. However, a further understanding of the significance of these autoantibodies has been hampered by limitations in accessing human subjects in a preclinical or early asymptomatic stage. To overcome this limitation, we have taken advantage of transgenic mice with abrogated transforming growth factor-ß signalling in T cells (dnTGF-ßRII) that develop histological features of PBC as well as the same AMA specificity. We studied these mice for serum ANA, including specific autoantibodies against gp210 and sp100. We further examined sera from dnTGF-ßRII mice with concurrent deletions of the genes encoding interleukin (IL)-12p35, IL-12p40, IL-23p19, IL-17, IL-6, interferon (IFN)-γ or tumour necrosis factor (TNF)-α. Sera from all the dnTGF-ßRII mouse lines contained antibodies against gp210 and sp100. Of significance, mice with germline deletions of the genes encoding IL-12p40, IL-23p19, IL-17, IL-6 and TNF-α had significantly lower titres of anti-gp210 antibodies. These results provide a platform to dissect the mechanisms of gp210 and sp100 autoantibody production in dnTGF-ßRII mice as well as to study the possible role of ANA in the pathophysiology of PBC.

The Scottish-Finnish-Swedish PARTNER study of taprostene versus placebo treatment in patients with critical limb ischemia.

AIM: Atherosclerotic peripheral arterial disease is a major health problem in the western world, often manifested as intermittent claudication, affecting 10-20% males above 60 years. Ischemic complications can lead to rest pain, ulceration and gangrene. The treatment of choice for critical limb ischemia (CLI) is vascular reconstruction or endovascular interventions. Medical management with vasodilator antiplatelet prostaglandins, could be considered in patients unsuitable for surgery. Long term follow-up on previous prostaglandin studies has been insufficient to evaluate amputation rates. Hence this study evaluated safety and longer term efficacy of taprostene sodium, a prostacyclin (PGI2) analogue in CLI. The aim of this study was to determine whether Taprostene sodium, a PGI2 analogue, was a safe and effective treatment for CLI. METHODS: This paper reports the data from the Scottish-Finnish-Swedish PARTNER Study Group which consisted of a double-blind placebo controlled multi-centre study evaluating Taprostene compared to placebo. The primary endpoints were pain relief and early ulcer healing response at the end of the four week infusion phase and amputation at six months follow-up. The patients were randomly allocated to receive taprostene or placebo in a two to one randomization of active versus placebo. A total of 111 patients with CLI were recruited. Taprostene was given twice a day over two 2 hour periods for four weeks. The early response was evaluated at the end of the four week infusion phase. In patients with rest pain without ulceration, a positive response was complete pain relief without any requirement for analgesic therapy. However in patients with ulceration, a positive response was defined as a decrease in the ulcer size by >30%. Amputation scores were compared at the end of the 6 months follow-up period for all participants. RESULTS: Seventy-four patients received taprostene and 37 placebo. Overall, 61 male patients were enrolled in the study along with 50 females with 11% more women in the taprostene (active) group. For both patients with and without ulcers there was no statistically significant difference noted in the early response between those receiving taprostene and those receiving placebo infusion. The percentage of patients without any amputations was 43% in the taprostene group compared to 38% in the control group at the end of six months; however, these results were not statistically significant. CONCLUSION: Although a reasonable number of patients enrolled in the study it has not been possible to demonstrate any statistically significant benefit of taprostene over placebo. This may be due to more patients with risk factors for peripheral artery disease (PAD) such as hypertension, diabetes mellitus and cigarette smoking in the actively treated group and also due the increased number of women in the active group who are known to generally respond less favourably to antiplatelet agents.

Sexual dimorphism in autoimmune disease.

We briefly survey the concept of autoimmunity and nominate the range of autoimmune diseases that include multisystemic and organ-specific disorders, and cite prevalences of autoimmune diseases in males and females, in humans and in experimental animals. Most human autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and autoimmune thyroid disease, have an increased incidence and prevalence in females, but a few others such as autoimmune diabetes, the Guillain Barré syndrome (GBS) and psoriasis are increased in males. Animal models of autoimmunity show an equivalent sexual dimorphism. The possible reasons for the differing incidence and prevalence of autoimmune diseases in females and males engage our attention. Environmental exposures may differ for females and males. There are innate differences in the function of the female and male immune systems, and there is some evidence for differences between females and males in the ability of a target organ for autoimmunity to withstand damage. In seeking reasons for these differences, we review the role of sex hormones in immunity and include results of trials of hormone therapy in autoimmune diseases. The association of autoimmunity and pregnancy, a female-specific condition, is discussed, and the claimed effects of lymphoid cell microchimerism on provocation of autoimmunity are reviewed. Genetic predisposition is an important factor in autoimmune disease and we particularly focus on genes on the X and Y chromosomes, the role of X chromosome inactivation, and the interaction of the sex of the patient with other genetic factors. The possible role of epigenetic mechanisms, including environmental influences, is then surveyed. We assert that sex is a vital variable that must be considered in all immunological studies, as it should be at all levels of biological research.

Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization.

Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC-E2) leads to an anti-mitochondrial antibody response and autoimmune cholangitis, similar to human primary biliary cirrhosis (PBC). We have suggested that this loss of tolerance can be induced either via chemical xenobiotic immunization or exposure to select bacteria. Our work has also highlighted the importance of genetic susceptibility. Using the non-obese diabetic (NOD) congenic strain 1101 (hereafter referred to as NOD.1101 mice), which has chromosome 3 regions from B6 introgressed onto a NOD background, we exposed animals to 2-octynoic acid (2OA) coupled to bovine serum albumin (BSA). 2OA has been demonstrated previously by a quantitative structural activity relationship to react as well as or better than lipoic acid to anti-mitochondrial antibodies. We demonstrate herein that NOD.1101 mice immunized with 2OA-BSA, but not with BSA alone, develop high titre anti-mitochondrial antibodies and histological features, including portal infiltrates enriched in CD8(+) cells and liver granulomas, similar to human PBC. We believe this model will allow the rigorous dissection of early immunogenetic cause of biliary damage.

Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study.

AIMS: To compare (i) the prevalence and incidence of chronic complications and (ii) cardiac and all-cause mortality in community-based patients with latent autoimmune diabetes in adults (LADA) with those in Type 2 diabetic patients without antibodies to glutamic acid decarboxylase (GAD). METHODS: Of the 1294 patients with clinically-defined Type 2 diabetes recruited to the longitudinal, observational Fremantle Diabetes Study between 1993 and 1996, 1255 (97%) had GAD antibodies measured at baseline. Complications were ascertained using standard criteria in patients returning for annual assessments until November 2001. Data on hospital admissions and mortality were available to the end of June 2006. Cox proportional hazards modelling was used to determine independent predictors of first occurrence of complications and cardiac and all-cause mortality. RESULTS: Forty-five (3.6%) subjects had LADA. Compared with the GAD antibody-negative patients, they had a similar prevalence and incidence of coronary heart (P = 0.48 and 0.80, respectively) and cerebrovascular (P = 0.64 and 0.29) disease and cardiac and all-cause mortality (P = 0.62 and 0.81, respectively). There was also a similar prevalence and incidence of retinopathy (P = 0.22 and 0.64, respectively) and neuropathy (P = 0.25 and 0.95), but microalbuminuria was less frequent both at baseline and during follow-up in the LADA subgroup in unadjusted models (P = 0.046) and after adjustment for other risk factors (P = 0.014 and 0.013). CONCLUSIONS: Except for a lower prevalence and incidence of nephropathy, LADA patients have a similar risk of complications and death to patients with clinically-diagnosed Type 2 diabetes without GAD antibodies. Cardiovascular risk factor management in LADA should, therefore, be as intensive as that for GAD antibody-negative patients.

An actin-myosin functional assay for analysis of smooth muscle (anti-microfilament) autoantibodies in human plasma.

The detection of serum autoantibodies to smooth muscle (SMA) on rodent gastric mucosa by indirect immunofluorescence (IIF) has long been an immunodiagnostic marker for autoimmune hepatitis type 1 (AIH-1). The reactive antigenic moieties are cytoskeletal proteins which include polymeric F-actin as judged by the staining of microfilaments of tissue by IIF. However, their specificity for actin in AIH-1 can be and usually is uncertain. Using an in vitro functional assay, we compared the effects of Fab fragments of immunoglobulin (IgG) prepared from SMA-positive plasma from two patients with the effects of Fabs from 10 healthy subjects. Fabs are incorporated into an assay where actin (the putative antigen) activates skeletal muscle heavy meromyosin (HMM) ATPase activity. The data from these functional assays provide new insights into the significance of anti-microfilament assays in the diagnosis, and perhaps also pathogenesis, of AIH-1.

A randomised, split-face comparison of facial hair removal with the alexandrite laser and intense pulsed light system.

INTRODUCTION: Despite the high incidence of polycystic ovary syndrome (PCOS) in women attending for facial hair removal there are few studies looking specifically at this patient group. We carried out a split-face study directly comparing the efficacy of a 3 milliseconds pulse duration alexandrite laser with the Lumina IPL system in 38 women with PCOS. MATERIALS AND METHODS: Each patient underwent six treatments using both systems, with 1, 3 and 6 months follow-up. Hair counts, hair-free intervals and patient satisfaction were recorded for all patients. RESULTS: After six treatments, alexandrite laser treatment resulted in longer median hair-free intervals when compared to IPL (7 weeks vs. 2 weeks; P < 0.001). Decrease in hair counts was significantly larger on the Alexandrite side compared to the IPL side at 1, 3 and 6 months (52%, 43% and 46% vs. 21%, 21% and 27%; P < 0.001). Patient satisfaction scores, using linear analogue scales (LAS), at 1, 3 and 6 months were significantly higher for the alexandrite laser than the IPL (8.7, 7.8 and 7.7 vs. 5.7, 5.1 and 5.1; P < or = 0.002). CONCLUSIONS: The alexandrite laser resulted in significantly longer hair-free intervals, a larger reduction in hair counts and greater patient satisfaction than the IPL and appeared to be more effective in this patient group. It is clear from the results in this study that the GentleLase alexandrite laser is more effective at reducing facial hirsutism in women with PCOS than the Lumina IPL. It is probable that this is due to the specific wavelength, short pulse duration and single pulse delivery of the GentleLase alexandrite laser, resulting in more follicular destruction than the IPL.

GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77.

AIMS/HYPOTHESIS: Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with autoantibodies to islet proteins developing in older patients who have no immediate requirement for insulin therapy. Markers of its clinical course are uncharacterised. The aim of this study was to determine whether persistence of, or changes in, GAD65 autoantibodies (GADAs) in the LADA patients who participated in the United Kingdom Prospective Diabetes Study (UKPDS) were associated with disease progression or insulin requirement. METHODS: GADA levels and their relative epitope reactivities to N-terminal, middle and C-terminal regions of human GAD65 were determined in 242 UKPDS patients who were GADA-positive at diagnosis; samples taken after 0.5, 3 and 6 years of follow-up were tested using a radiobinding assay. Comparisons were made of GADA status with clinical details and disease progression assessed by the requirement for intensified glucose-lowering therapy. RESULTS: GADA levels fluctuated between 0.5 and 6 years but persisted in 225 of 242 patients. No association of GADA levels with disease progression or insulin requirement was observed. Antibody reactivity was directed to C-terminal and middle epitopes of GAD65 in >70% patients, and the N-terminal in <9%. There were no changes in epitope reactivity pattern over the 6 year follow-up period, nor any association between epitope reactivity and insulin requirement. CONCLUSIONS/INTERPRETATION: GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated with disease progression.

Assessment of burn depth: a prospective, blinded comparison of laser Doppler imaging and videomicroscopy.

INTRODUCTION AND AIMS: There is a need, both in clinical and research settings, for an affordable, objective method of assessing burn depth. This study compares burn depth assessment by videomicroscopy with laser Doppler imaging (LDI) in patients with dermal burns. The videomicroscope is inexpensive compared to LDI, and can visualise the dermal capillary structure, therefore potentially allowing objective assessment of dermal burn injuries. METHODS: Patients admitted <72 h post-injury were included in the trial. Blinded LDI and videomicroscopy assessments were carried out. The patients were then followed up to one of three end-points: primary healing without surgery; early surgery; delayed healing and subsequent split skin grafting. The incidence of infection was also noted. RESULTS: Twenty-seven burn wounds were examined. In superficial partial thickness injuries, the videomicroscope reliably demonstrated an intact or nearly intact dermal vascular structure, progressing through to large amounts of capillary destruction and haemoglobin deposition in deep partial thickness injuries and complete destruction in full thickness injuries. The videomicroscope findings correlated strongly with both those of the LDI (p<0.001) and with clinical outcome (p<0.001). DISCUSSION: The videomicroscope is capable of accurately and objectively assessing burn depth. The results correlated well with both the clinical outcome and the laser Doppler findings. In addition, videomicroscopy is significantly cheaper than LDI and avoids several of the disadvantages of LDI.

Recurrence of spider naevi following treatment with 585 nm pulsed dye laser.

During a 2-year period 201 patients underwent treatment for spider naevi with a 585nm pulsed dye laser at Canniesburn Hospital Laser Suite. Patients were treated with a either single or double pulse technique. Of these patients 191 (95%) had a successful result, with clearance in a mean of 1.8 treatments (range, 1-7). There was no significant difference between the two treatment protocols in terms of probability of clearing the lesion or number of treatments required. These 191 patients were contacted by postal survey to determine their long-term results. The mean duration of follow-up was 37.9 months (range, 27-51 months). Response rate to the survey was 73%, 139 patients. Fifty patients (36%) had suffered recurrence of their spider naevi in the same site. There was no correlation found between the risk of recurrence and the site, number of treatments received, size and characteristics of the spider naevus, or treatment protocol used. The risk of recurrence increased with increasing age and was higher for peripheral facial lesions. The most common time of recurrence was between 6 and 18 months with 48% of recurrences occurring during this period. Existing published series, which have demonstrated low recurrence rates, have either had low numbers of patients or short follow-up periods of less than 6 months.

Laser hair removal in women with polycystic ovary syndrome.

UNLABELLED: Polycystic ovary syndrome (PCOS) is one of the most common reasons for women to present seeking removal of facial hair, particularly within the UK National Health Service (NHS). In the NHS, there is geographical variation in the number of laser treatments available to women with PCOS, with some units limiting patients to six treatments whilst others allow unlimited treatments. This study aims to assess the effect of number of treatments on women with PCOS. METHODS: This study prospectively assessed hair counts, hair-free intervals and patient satisfaction in 60 women with PCOS undergoing 3ms pulse duration alexandrite laser treatment. RESULTS: Following six treatments there was a mean 31+/-38% reduction in hair counts (mean+/-SD; P=0.001). Mean hair-free interval (HFI) increased steadily with treatment, from 1.9 weeks after six treatments to 4.3 weeks after 10 treatments (P=0.001). From the postal questionnaire, after an average of 12 treatments, 31% of patients had a HFI longer than 6 weeks compared to only 2.6% after six treatments (P=0.003). Overall, despite the low hair count reductions, 95% of patients were satisfied with treatment. CONCLUSION: In women with PCOS, laser treatment is associated with a poorer than expected reduction in hair counts and HFI following treatment. However, offering more than six treatments does have additional benefits in terms of prolonging HFI and overall patient satisfaction with treatment is very high.

History of immunology in Australia: events and identities.

Immunology originated in Europe during the latter 1900s, and applications can be discerned in colonial Australia. The actual beginnings of immunology in Australia followed Burnet's enunciation of two fundamental principles: natural immune tolerance as an acquired characteristic in 1948 and clonal selection theory in 1957. Laboratory and clinical immunology flourished at various centres from the 1950s. The Australian Society of Immunology was founded in 1971. The merger of clinical immunology with allergy in 1991 created the Australian Society of Clinical Immunology and Allergy, exemplary for the reamalgamation of these related specialties. Australian immunology over the past 50 years has become recognized nationally and abroad as a highly visible component of the academic, research and biomedical scene and is still on a rising trajectory.

The effect of ambient temperature on capillary vascular malformations.

BACKGROUND: Following pulsed dye laser (PDL) treatment of capillary vascular malformations (CMs), the capillaries left behind tend to be smaller and deeper. The PDL is most effective against capillaries over 50 microm, suggesting that clearance of CM could be improved by inducing capillary vasodilation of the smaller remaining capillaries. However, there are reduced perivascular nerves within CMs, implying that autonomic innervation to these capillaries may be abnormal. OBJECTIVES: To investigate whether CM capillaries will vasodilate in response to autonomic stimulation by raising ambient temperature. METHODS: Ten patients with untreated CMs and nine with previously laser-treated CMs were studied as ambient temperature was increased from 20 degrees C to 28 degrees C. The following measurements were taken at 2 degrees C intervals: skin blood flow (SBF); capillary diameter and depth; CM colour; and skin and core temperatures. RESULTS: All the subjects studied demonstrated superficial capillary vasodilation and increased SBF as the ambient temperature was raised from 20 degrees C to 28 degrees C. Mean+/-SEM capillary diameter increased from 66+/-7 microm to 110+/-13 microm (P<0.001) in the untreated group, compared with an increase from 28+/-5 microm to 70+/-14 microm (P<0.001) in the treated group. Mean+/-SEM SBF increased from 427.2+/-98.2 perfusion units (PU) to 580.9+/-92.7 PU (P<0.01) in the untreated group, compared with an increase from 201.3+/-28.4 PU to 458.1+/-53.7 PU (P<0.05) in the treated group. CONCLUSIONS: Superficial capillary vasodilation within CM is achievable by raising ambient temperature, including in those patients resistant to PDL treatment, potentially allowing further clearance of these lesions.

IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71).

AIMS/HYPOTHESIS: Established autoimmune markers of type 1 diabetes, including islet cell autoantibodies (ICA) and autoantibodies to glutamic acid decarboxylase (GADA) have been used to screen people presenting with type 2 diabetes for latent autoimmune diabetes in adults. We have examined the prevalence of autoantibodies to protein tyrosine phosphatase isoforms IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA) in a cohort of adult UKPDS patients thought to have type 2 diabetes, and investigated the possible role of these autoantibodies in predicting requirement for insulin therapy. METHODS: IA-2A and IA-2betaA were measured by a validated radioimmunoassay with human recombinant autoantigens in 4,169 white Caucasian patients aged 25-65 years and newly diagnosed with type 2 diabetes. The clinical requirement for insulin therapy within 6 years was examined in 2,556 patients not randomised to insulin. RESULTS: IA-2A and IA-2betaA were present in 2.2 and 1.4%, respectively, of these patients. IA-2A were more prevalent in younger patients (p for trend <0.00001), more often associated with the HLA-DR4 allele (26.3 vs 8.0%, p<0.0001), and their presence increased the likelihood of insulin therapy requirement within 6 years from diagnosis [relative risk (95%CI) 12.2 (9.8-15.3)]. The presence of IA-2A together with GADA increased the relative risk of requiring insulin therapy from 5.4 (4.1-7.1) for GADA alone to 8.3 (3.7-18.8) and the corresponding positive predictive value from 33 to 50%. CONCLUSIONS/INTERPRETATION: In type 2 diabetes, the presence of IA-2A is infrequent, associated with the HLA-DR4 haplotype, and highly predictive of future need for insulin therapy. The measurement of IA-2betaA does not provide additional information.

Islet autoantibodies in clinically diagnosed type 2 diabetes: prevalence and relationship with metabolic control (UKPDS 70).

AIMS/HYPOTHESIS: We examined the prevalence of islet autoantibodies and their relationship to glycaemic control over 10 years in patients diagnosed clinically with new-onset type 2 diabetes. METHODS: Patient clinical characteristics and autoantibody status were determined at entry to the UK Prospective Diabetes Study (UKPDS) before randomisation to different glucose control policies. Patients were followed for 10 years. RESULTS: Data available on 4,545 of the 5,102 UKPDS patients showed that 11.6% had antibodies to at least one of three antigens: islet cell cytoplasm, glutamic acid decarboxylase and islet autoantibody 2A (IA-2A). Autoantibody-positive patients were younger, more often Caucasian and leaner, with lower beta cell function and higher insulin sensitivity than autoantibody-negative patients. They also had higher HbA1c, and HDL-cholesterol levels, and lower blood pressure, total cholesterol and plasma triglyceride levels. Despite relative hyperglycaemia, autoantibody-positive patients were less likely to have the metabolic syndrome (as defined by the National Cholesterol Education Program Adult Treatment Program III), reflecting a more beneficial overall risk factor profile. Of 3,867 patients with post-dietary run-in fasting plasma glucose (FPG) values between 6.0 and 14.9 mmol/l and no hyperglycaemic symptoms, 9.4% were autoantibody-positive, compared with 25.1% of 678 patients with FPG values of 15.0 mmol/l or higher, or hyperglycaemic symptoms. In both groups, no differences were seen between those with and without autoantibodies in changes to HbA1c over time, but autoantibody-positive patients required insulin treatment earlier, irrespective of the allocated therapy (p<0.0001). CONCLUSIONS/INTERPRETATION: Autoantibody-positive patients can be treated initially with sulphonylurea, but are likely to require insulin earlier than autoantibody-negative patients.

Humanism and the suffering of the people.

Abstract Humanism includes, among its many contexts, the ideal of the universal perfection of health. Procedures for alleviation of disease existed through all epochs of human history, but efficacy was mostly lacking. The prototypic humanism of the Renaissance (ad 1300-1600) scarcely involved the medical -sciences other than human anatomy. The Enlightenment of the seventeenth century included discovery of the circulation of the blood, and applications of microscopy. Discoveries relevant to medical practice began in the nineteenth century, ushered in by vaccination and the germ theory of disease. This 200-year period saw a transformation of human health according to the surrogate marker of increased life--expectancy. This has been variously attributed to: (i) increased prosperity following the industrial revolution, (ii) efforts of humanistic social and public health reformers and, more recently, (iii) advances in medical science. Yet the beneficiaries remain a minority of the world's population. The nexus between poverty, illness and low life-expectancy between and within nations is the major challenge for the future. Contemporary science is providing ever-expanding knowledge on means to achieve the goal of perfection of human health, but the need for humanism is as great as at any previous age. Fortunately, however, the targets are more clearly visible than during the periods of poverty, plagues and pestilence of the past.