On the Bluish Appearance of Veins

The bluish appearance of veins located immediately beneath the skin has long been a topic of interest for biomedical optics researchers. Despite this interest, a thorough identification of the specific optical processes responsible for this phenomenon remains to be achieved. In this paper, we employ controlled in silico experiments to address this enduring open problem. Our experiments, which are supported by measured data available in the scientific literature, are performed using first-principles models of light interaction with human skin and blood. Using this investigation approach, we quantitatively demonstrate that Rayleigh scattering caused by collagen fibrils present in the papillary dermis, a sublayer of the skin, can play a pivotal role in the bluish appearance of veins as suggested by previous works in this area. Moreover, taking colour perception aspects also into account, we systematically assess the effects of variations in fibril radius and papillary dermis thickness on the coloration of veins under different illuminants. Notably, this assessment indicates that Rayleigh scattering elicited by reticulin fibrils, another type of fibril found in the papillary dermis, is unlikely to significantly contribute to the bluish appearance of veins. By strengthening the current understanding about light attenuation mechanisms affecting the appearance of skin and blood, our investigation contributes for the development of more effective technologies aimed at the noninvasive measurement of the physiological properties of these tissues

On Skin Cyanotic Appearances and Spectral Responses Elicited by Methemoglobinemia and Sulfhemoglobinemia

Methemoglobinemia and sulfhemoglobinemia are potentially life-threatening blood disorders characterized by similar symptoms and markedly distinct treatment procedures. In this thesis, we investigate the causal relationship between these disorders and the onset of cyanosis (purple or bluish skin coloration). More specifically, we perform controlled experiments to elicit cyanotic appearances resulting from different severity levels of these disorders and varying physiological conditions. We note that such experiments cannot be induced in living subjects without posing risks to their health. Accordingly, we have resorted to an in silico experimental approach supported by biophysical data reported in the biomedical literature. Besides bringing new insights about cyanotic chromatic variations elicited by methemoglobinemia and sulfhemoglobinemia, our investigation provides the basis for the proposition of a cost-effective protocol for the noninvasive detection and differentiation of these disorders. Our experimental results indicate that its sensitivity range exceeds the range of similar technologies, which are in general associated with high operational costs. We believe that these aspects make the proposed protocol particularly suitable for incorporation into noninvasive disease screening/diagnostic systems, particularly those deployed at the point of care of medical settings with limited access to laboratory resources

A Clinical Study of the Cutaneous Manifestations of Chronic Renal Failure.

The kidney and the skin are the two large networks of the body with their abundant blood supply, far in excess of their nutritional demands, the former for the constancy of the milieu interior and the latter maintaining mainly homeostasis. No wonder therefore, that they share many diseases and reflect mutually one another’s pathology which should be made use of by the clinician. Scientific and technologic improvements during the second-half of the 20th century have provided renal replacement therapy as a life-sustaining option for many individuals who otherwise may have died. For each year of the last 10 years, the number of individuals with end stage renal disease has grown approximately 20,000 per year. Cutaneous examination of patients with end stage renal disease has shown that 50 – 100% of the patients have at least one dermatologic condition. In addition to end stage renal disease, Uremia and conditions associated with replacement therapy are fraught with numerous and, often relatively unique cutaneous disorders. AIMS : 1. To study the various cutaneous manifestations and their incidence in patients with chronic renal failure. 2. To study the age and sex incidence of the individual cutaneous manifestations. 3. To study the incidence and types of cutaneous infections in chronic renal failure. 4. To study the treatment-related (medical and dialysis) dermatologic manifestations of chronic renal failure. 5. To correlate between the skin manifestations of systemic disorders with chronic renal failure. CONCLUSION: This clinical study of cutaneous manifestations of chronic renal failure was done during the period December ’03 to December ‘05 revealed the following 1. Most of the specific cutaneous manifestations of chronic renal failure were seen in this study. Pruritus and xerosis were the most common among the specific cutaneous manifestations of chronic renal failure. Pigmentary alterations and nail abnormalities were the next. Mucosal and hair abnormalities were noted in good percentage of cases. Nearly 10% had perforating dermatosis and purpura. Interesting findings noted in this study were digital gangrene, poor wound healing, and restless leg syndrome. 2. Skin changes due to treatment reported were arteriovenous shunt dermatitis, keratotic pits of palms in small percentage and blue nails in a patient during hemodialysis, other than pruritus and pigmentary alterations. 3. Cutaneous infections and infestations were seen in 43.8 % of the cases. This high incidence could be due to impaired immunity resulting in increased susceptibility to infections in chronic renal failure patients. Fungal infections were the most common, followed by viral, bacterial and parasitic infestations. 4. Associated skin changes of systemic diseases helped in finding varying etiologies of chronic renal failure such s diabetes mellitus, systemic lupus erythematosus, scleroderma, vasculitis, Henoch schonlein purpura, idiopathic thrombocytopenic purpura. A case of cortical medullary disease in Ellis van creveld syndrome was reported with cutaneous changes. A case of tuberous sclerosis with renal involvement and skin changes was seen. Other associated skin changes were not related to the etiology and were found to be just coincidental

Дитячі інфекційні хвороби у практиці сімейного лікаря

Навчально-методичний посібник складений згідно з типовим навчальним планом та програмою для підготовки іноземних студентів медичних закладів вищої освіти для циклу «Дитячі інфекційні хвороби». Цей навчально-методичний посібник написаний англійською мовою і присвячений питанням етіології, епідеміології, клініки та диференційної діагностики найбільш частих дитячих інфекційних хвороб, наведені алгоритми діагностики та терапії, згідно з протоколами лікування, що затверджені МОЗ України. Назви розділів автори підібрали у відповідності з тематичним планом для підготовки іноземних студентів медичних закладів вищої освіти. Посібник містить запитання для самоконтролю, тести, задачі та розбір історій хвороб дітей, що лікувались у дитячому відділенні ПОКІЛ для більш глибокого засвоєння матеріалу; The teaching manual is compiled according to a typical curriculum and a program for the preparation of foreign students of medical institutions of higher education for the cycle "Children's Infectious Diseases". This teaching manual is written in English and is devoted to the issues of etiology, epidemiology, clinics and differential diagnostics of the most common infectious diseases of children, diagnostic algorithms and therapies are given in accordance with the treatment protocols approved by the Ministry of Health of Ukraine. The titles of the sections were chosen by the authors in accordance withthe thematic plan for thepreparation of foreign students of medical institutions of highereducation. The manual contains questions for self-control, tests, tasks and analysis of children's diseaserecords that were treated at the children's department for a deeper assimilation of the material

The Role of Connective Tissue Growth Factor (CTGF) in Fibrosis Associated With Intestinal Neuroendocrine Tumors

Carcinoid tumors of the small bowel often present with fibrosis in the peritumoral tissues, distant in the heart or lungs, and locally in the peritoneal cavity. The mechanism of the fibroblastic lesions in patients with small bowel carcinoids is unclear and their timely diagnosis impossible. There exists no test to determine the risk of fibrosis, detect its presence, or monitor its progression once discovered. Furthermore, no current therapy protects against such fibrosis. We have proposed that CTGF, a mediator of the profibrotic activities of TGFâ1 (a known regulator of fibrosis)is directly involved in the genesis of ileal carcinoid-related fibrosis. The aim of this study was to assess the potential correlation of serum and tissue CTGF with the diagnosis of carcinoid-related fibrosis. Serum and tissue samples from patients with GI carcinoids, other GI and extra-GI malignancies, and control patients were collected prospectively. A GI carcinoid tissue microarray (TMA) was stained immunohistochemically with anti-CTGF, semiquantitatively measured, and analyzed for correlation with clinical fibrosis. Significantly higher serum CTGF levels were found in patients with ileal carcinoids than in patients with gastric ECL cell carcinoids (the latter of which are not associated with fibrosis) and control patients. Our results demonstrated that CTGF protein is over-expressed in small bowel carcinoid tumors associated with fibrosis and that the secreted protein is stable and detectable in patient serum. The correlation of CTGF with TGFâ1 suggests that CTGF is a co-secreted fibrotic factor. Since the relationship of CTGF to fibrosis is well defined, this cytokine may be involved in the genesis of ileal carcinoid-related fibrosis. The detection of elevated levels may provide a diagnostic opportunity to predict fibrosis and pre-empt its local and systemic complications. Furthermore, CTGF may represent a therapeutic target for management of fibrosis-related complications in patients with carcinoid tumors

The Genetics of Basal Cell Carcinoma of the Skin

BCC is the commonest cancer in European-derived populations and Australia has the highest recorded incidence in the world, creating enormous individual and societal cost in management of this disease. The incidence of this cancer has been increasing internationally, with evidence of a 1 to 2% rise in incidence in Australia per year over the last two decades. The main four epidemiological risk factors for the development of BCC are ultraviolet radiation (UVR) exposure, increasing age, male sex, and inability to tan. The pattern and timing of UVR exposure is important to BCC risk, with childhood and intermittent UVR exposure both associated with an increased risk. The complex of inherited characteristics making up an individual’s ‘sun sensitivity’ is also important in determining BCC risk. Very little is known about population genetic susceptibility to BCC outside of the rare genodermatosis Gorlin syndrome. Mutations in the tumour suppressor gene patched (PTCH) are responsible for this BCC predisposition syndrome and the molecular pathway and target genes of this highly conserved pathway are well described. Derangments in this pathway occur in sporadic BCC development, and the PTCH gene is an obvious candidate to contribute to non-syndromic susceptibility to BCC. The melanocortin 1 receptor (MC1R) locus is known to be involved in pigmentary traits and the cutaneous response to UVR, and variants have been associated with skin cancer risk. Many other genes have been considered with respect to population BCC risk and include p53, HPV, GSTs, and HLAs. There is preliminary evidence for specific familial aggregation of BCC, but very little known about the causes. 56 individuals who developed BCC under the age of 40 in the year 2000 were recruited from the Skin and Cancer Foundation of Australia’s database. This represents the youngest 7 – 8% of Australians with BCC from a database that captures approximately 10% of Sydney’s BCCs. 212 of their first degree relatives were also recruited, including 89 parents and 123 siblings of these 56 probands. All subjects were interviewed with respect to their cancer history and all reports of cancer verified with histopathological reports where possible. The oldest unaffected sibling for each proband (where available) was designated as an intra-family control. All cases and control siblings filled out a questionnaire regarding their pigmentary and sun sensitivity factors and underwent a skin examination by a trained examiner. Peripheral blood was collected from these cases and controls for genotyping of PTCH. All the exons of PTCH for which mutations have been documented in Gorlin patients were amplified using PCR. PCR products were screened for mutations using dHPLC, and all detectable variants sequenced. Prevalence of BCC and SCC for the Australian population was estimated from incidence data using a novel statistical approach. Familial aggregation of BCC, SCC and MM occurred within the 56 families studied here. The majority of families with aggregation of skin cancer had a combination of SCC and BCC, however nearly one fifth of families in this study had aggregation of BCC to the exclusion of SCC or MM, suggesting that BCCspecific risk factors are also likely to be at work. Skin cancer risks for first-degree relatives of people with early onset BCC were calculated: sisters and mothers of people with early-onset BCC had a 2-fold increased risk of BCC; brothers had a 5-fold increased risk of BCC; and sisters and fathers of people with early-onset BCC had over four times the prevalence of SCC than that expected. For melanoma, the increased risk was significant for male relatives only, with a 10-fold increased risk for brothers of people with early-onset BCC and 3-fold for fathers. On skin examination of cases and controls, several phenotypic factors were significantly associated with BCC risk. These included increasing risk of BCC with having fair, easyburning skin (ie decreasing skin phototype), and with having signs of cumulative sun damage to the skin in the form of actinic keratoses. Signs reflecting the combination of pigmentary characteristics and sun exposure - in the form of arm freckling and solar lentigines - also gave subjects a significantly increased risk BCC. Constitutive red-green reflectance of the skin was associated with decreased risk of BCC, as measured by spectrophotometery. Other non-significant trends were seen that may become significant in larger studies including associations of BCC with propensity to burn, moderate tanning ability and an inability to tan. No convincing trend for risk of BCC was seen with the pigmentary variables of hair or eye colour, and a non-significant reduced risk of BCC was associated with increasing numbers of seborrhoeic keratoses. Twenty PTCH exons (exons 2, 3, 5 to 18, and 20 to 23) were screened, accounting for 97% of the coding regions with published mutations in PTCH. Nine of these 20 exons were found to harbour single nucleotide polymorphisms (SNPs), seen on dHPLC as variant melting curves and confirmed on direct sequencing. SNPs frequencies were not significantly different to published population frequencies, or to Australian general population frequencies where SNP database population data was unavailable. Assuming a Poisson distribution, and having observed no mutations in a sample of 56, we can be 97.5% confident that if there are any PTCH mutations contributing to early-onset BCC in the Australian population, then their prevalence is less than 5.1%. Overall, this study provides evidence that familial aggregation of BCC is occurring, that first-degree relatives are at increased risk of all three types of skin cancer, and that a combination of environmental and genetic risk factors are likely to be responsible. The PTCH gene is excluded as a major cause of this increased susceptibility to BCC in particular and skin cancer in general. The weaknesses of the study design are explored, the possible clinical relevance of the data is examined, and future directions for research into the genetics of basal cell carcinoma are discussed

The Genetics of Basal Cell Carcinoma of the Skin

BCC is the commonest cancer in European-derived populations and Australia has the highest recorded incidence in the world, creating enormous individual and societal cost in management of this disease. The incidence of this cancer has been increasing internationally, with evidence of a 1 to 2% rise in incidence in Australia per year over the last two decades. The main four epidemiological risk factors for the development of BCC are ultraviolet radiation (UVR) exposure, increasing age, male sex, and inability to tan. The pattern and timing of UVR exposure is important to BCC risk, with childhood and intermittent UVR exposure both associated with an increased risk. The complex of inherited characteristics making up an individual’s ‘sun sensitivity’ is also important in determining BCC risk. Very little is known about population genetic susceptibility to BCC outside of the rare genodermatosis Gorlin syndrome. Mutations in the tumour suppressor gene patched (PTCH) are responsible for this BCC predisposition syndrome and the molecular pathway and target genes of this highly conserved pathway are well described. Derangments in this pathway occur in sporadic BCC development, and the PTCH gene is an obvious candidate to contribute to non-syndromic susceptibility to BCC. The melanocortin 1 receptor (MC1R) locus is known to be involved in pigmentary traits and the cutaneous response to UVR, and variants have been associated with skin cancer risk. Many other genes have been considered with respect to population BCC risk and include p53, HPV, GSTs, and HLAs. There is preliminary evidence for specific familial aggregation of BCC, but very little known about the causes. 56 individuals who developed BCC under the age of 40 in the year 2000 were recruited from the Skin and Cancer Foundation of Australia’s database. This represents the youngest 7 – 8% of Australians with BCC from a database that captures approximately 10% of Sydney’s BCCs. 212 of their first degree relatives were also recruited, including 89 parents and 123 siblings of these 56 probands. All subjects were interviewed with respect to their cancer history and all reports of cancer verified with histopathological reports where possible. The oldest unaffected sibling for each proband (where available) was designated as an intra-family control. All cases and control siblings filled out a questionnaire regarding their pigmentary and sun sensitivity factors and underwent a skin examination by a trained examiner. Peripheral blood was collected from these cases and controls for genotyping of PTCH. All the exons of PTCH for which mutations have been documented in Gorlin patients were amplified using PCR. PCR products were screened for mutations using dHPLC, and all detectable variants sequenced. Prevalence of BCC and SCC for the Australian population was estimated from incidence data using a novel statistical approach. Familial aggregation of BCC, SCC and MM occurred within the 56 families studied here. The majority of families with aggregation of skin cancer had a combination of SCC and BCC, however nearly one fifth of families in this study had aggregation of BCC to the exclusion of SCC or MM, suggesting that BCCspecific risk factors are also likely to be at work. Skin cancer risks for first-degree relatives of people with early onset BCC were calculated: sisters and mothers of people with early-onset BCC had a 2-fold increased risk of BCC; brothers had a 5-fold increased risk of BCC; and sisters and fathers of people with early-onset BCC had over four times the prevalence of SCC than that expected. For melanoma, the increased risk was significant for male relatives only, with a 10-fold increased risk for brothers of people with early-onset BCC and 3-fold for fathers. On skin examination of cases and controls, several phenotypic factors were significantly associated with BCC risk. These included increasing risk of BCC with having fair, easyburning skin (ie decreasing skin phototype), and with having signs of cumulative sun damage to the skin in the form of actinic keratoses. Signs reflecting the combination of pigmentary characteristics and sun exposure - in the form of arm freckling and solar lentigines - also gave subjects a significantly increased risk BCC. Constitutive red-green reflectance of the skin was associated with decreased risk of BCC, as measured by spectrophotometery. Other non-significant trends were seen that may become significant in larger studies including associations of BCC with propensity to burn, moderate tanning ability and an inability to tan. No convincing trend for risk of BCC was seen with the pigmentary variables of hair or eye colour, and a non-significant reduced risk of BCC was associated with increasing numbers of seborrhoeic keratoses. Twenty PTCH exons (exons 2, 3, 5 to 18, and 20 to 23) were screened, accounting for 97% of the coding regions with published mutations in PTCH. Nine of these 20 exons were found to harbour single nucleotide polymorphisms (SNPs), seen on dHPLC as variant melting curves and confirmed on direct sequencing. SNPs frequencies were not significantly different to published population frequencies, or to Australian general population frequencies where SNP database population data was unavailable. Assuming a Poisson distribution, and having observed no mutations in a sample of 56, we can be 97.5% confident that if there are any PTCH mutations contributing to early-onset BCC in the Australian population, then their prevalence is less than 5.1%. Overall, this study provides evidence that familial aggregation of BCC is occurring, that first-degree relatives are at increased risk of all three types of skin cancer, and that a combination of environmental and genetic risk factors are likely to be responsible. The PTCH gene is excluded as a major cause of this increased susceptibility to BCC in particular and skin cancer in general. The weaknesses of the study design are explored, the possible clinical relevance of the data is examined, and future directions for research into the genetics of basal cell carcinoma are discussed

Non-invasive optical monitoring of free and bound oxygen in humans

Background: Possibilities of detecting oxygen - both in its free form, as gas in the lungs, and in its bound form, as oxygenated hemoglobin - have been explored in this thesis. Perfusion and oxygenation of vital organs (e.g., heart, brain and kidneys) may be severely compromised in critical illness or major trauma, which is why blood is rapidly diverted to those organs to improve chances of survival. Blood vessels in less important organs (e.g., skin, skeletal muscles and intestines) are constricted, leading to reduced regional perfusion and oxygenation in these organs. Non-invasive measurements of changes in tissue perfusion and oxygenation, in e.g., the forearm, might give an early indication of clinical deterioration. Preterm infants are very vulnerable patients. Their organs, in particular the lungs, are not fully developed, and the respiratory distress syndrome (RDS) frequently occurs. The intestines may be affected by necrotizing enterocolitis (NEC). Complementary diagnostic and surveillance methods of RDS and NEC are desirable. Aims: The overall aim of this thesis, which includes Studies I-IV, was to develop and evaluate non-invasive optical techniques, based on light at different wavelengths, to complement future bedside surveillance in critically illness or severe injury, for adults as well as for infants. Methods: Changes in tissue oxygenation by near-infrared spectroscopy (I-II), blood perfusion by laser Doppler imaging (I) and blood volume by tissue viability imaging (I) in skeletal muscle and skin were studied, and continuous-wave and timeresolved near-infrared spectroscopy were compared (II) in healthy volunteers subjected to various defined regional physiological perturbations. For the first time, gas in scattering media absorption spectroscopy (GASMAS) was used to detect alveolar water vapor (III-IV) and oxygen gas (IV), as well as intestinal water vapor (III) in newborn infants. Main results: Near-infrared spectroscopy, laser Doppler imaging and tissue viability imaging provided valuable information on physiological changes in the microcirculation (I). Continuous-wave and time-resolved near-infrared spectroscopy techniques were both able to determine changes in tissue oxygenation, but the time-resolved technique provided more realistic values with smaller inter-individual differences (II). Alveolar (III-IV) and intestinal signals of water vapor (III), were readily detected, together with alveolar signals of oxygen gas (IV), non-invasively in newborn infants. Conclusions: Optical techniques, being non-invasive and providing data in real-time, are attractive as potential tools for surveillance in critical illness or severe injury, in particular concerning the oxygenation. As an overall conclusion, we believe, that fully developed time-resolved near-infrared techniques have the potential to become an additional monitoring method of choice for surveillance of critically ill or severely injured patients. Likewise, GASMAS has great potential for future monitoring of critically ill preterm or full-term infants, and might, ultimately, reduce the current use of X-ray imaging in these most vulnerable patients

Occupational diseases: a guide to their recognition

Revised edition."Occupational diseases are discussed in terms of occupational health hazards. The purpose of the text is to make available information needed for timely recognition of symptoms of occupational diseases. The text covers routes of entry and modes of action, biological hazards, dermatoses, diseases of the airways, plant and wood hazards, chemical hazards, chemical carcinogens, pesticides, and such physical hazards as radiation, atmospheric variations, and oscillatory vibrations. Sources of consultation and references are included." - NIOSHTIC-2Edition for 1964 by the Institute under its earlier name, Division of Occupational Health.editors, Marcus M. Key ... [et al.] manuscript editor, Lorice Ede.Includes index.Bibliography: p. 534-556