Aulus Cornelius Celsus' De Medicina and His Contributions to Knowledge on Skin Diseases.

The book De Medicina by Aulus Cornelius Celsus was the first complete treatise about medicine written in Latin. We know little about his life. The monography consists of eight books describing all that was known within the whole sphere of medicine and surgery in the first century AD. In the introduction (proemium), he also described the history of medicine until his time and also delineated the treatment of diseases that may be dietetic, medication-based or surgical. The treatise describes approximately forty skin diseases in a concise and clear style.

Girolamo Mercuriale, the First Author of a Treatise on Skin Diseases.

Skin diseases are easily diagnosable by observation. Authors in ancient times already wrote on these diseases, if only succinctly. In the sixteenth century, Mercuriale, a famous Italian physician who taught in Padua, Bologna, and Pisa, wrote "The morbis cutaneis", the first book on the subject. In it, he presented a classification of skin diseases based on change of color, texture, and elevation. He described the opinion of the classic medical authors about the skin, its diseases, and how to treat those diseases. It was only two centuries later that Plenck, Willan, and his disciple Bateman introduced a better classification and terminology for these diseases.

History of venereal diseases from antiquity to the renaissance.

Sexually transmitted diseases (STDs), previously known as venereal diseases (VD), were present among the populations of antiquity as well as during the Middle Ages. Clay tablets from Mesopotamia, Egyptian papyri, along with mythology, paintings of erotic scenes, and presence of prostitutes give sufficient information to assume that some form of urethral and vaginal discharge, and also herpes genitalis were present among people at that time, and that these diseases were considered a divine punishment. Some passages of the Bible say much about the sexual behavior of the ancient Hebrews. The writings of the Greek and Roman physicians and of their satiric poets (Martial, Juvenal, Ovid) described diverse genital diseases. Celsus described various diseases of the genitals, that he called the "obscene parts". Galen made a strange description of the female genitals and coined the term gonorrhea - flow of semen. The ancient Chinese and Indian physicians also gave some account on the presence of venereal diseases in their books, and the temple sculptures depict their sexual life. During the Middle Ages, numerous physicians and surgeons from Europe as well as from Arabic countries wrote on local diseases of the genitals, describing chancres, condylomata, erosions, pustules, urethral and vaginal discharge, and their treatment. Some were aware that the alterations were connected with sexual activity. In spite the fact the Christian church propagated abstinence, the spread of venereal diseases was possible because the diffusion of prostitution, communal baths, and wars. During the 19th century, some of the physicians and historians, especially J. Rosenbaum, F. Buret, and E. Lancereaux believed syphilis was as old as mankind, whereas later authors had the opinion the disease appeared at the end of the 15th century.

Endemic syphilis in Europe.

Nonvenereal syphilis (endemic syphilis) has existed in Europe since the 16th century. Main characteristics of the disease are its presence for a longer time in a specific territory and its transmission regardless of age and sex, mainly extragenitally in unsanitary living conditions. Nonvenereal syphilis was described under different names in almost all regions of Europe. The primary genital chancre was absent, and lesions were most frequently found in the mouth and affected mostly children. The disease spread in rural areas with poor economic and hygienic conditions. The disease was eradicated in Europe in the 20th century, but it is still present in some rural regions of the Arabian Peninsula, Southwest Asia, and North Africa.

Syphilis and Scherlievo in Dalmatia.

The authors describe the emergence of syphilis in Dalmatia, the coastal part of Croatia, at the very end of the 15(th) and the beginning of the 16(th) century, its presence up to the 20(th) century, making reference to the most important physicians that tried to cure the new disease. The archives of Dalmatian towns, their statutes, some literary works, travel writers, physician books, and articles by historians of medicine contain data on syphilis in Dalmatia. Syphilis was first observed in Zadar (1500), Trogir (1501) and Dubrovnik (1502). Among the first physicians who treated patients in Dubrovnik were Mariano Santo and Amatus Lusitanus. The latter was the first to make prosthesis for the palate defect to cure tertiary syphilis lesions. According to the statutes of Dalmatia towns, each had one or more paid physicians and pharmacists. The Ottoman travel writer Evlija Celebi gave an account of syphilis in Dalmatia in the 17(th) century. At the end of the 18(th) century and during the 19(th) century, endemic syphilis known as morbus de Scherlievo and morbus Brenensis appeared in Dalmatia. Because of the numerous cases observed in the region, new hospitals were opened in Dalmatian towns and the patients were hospitalized. Among the physicians who were engaged in the fight against syphilis in the 19th century, mention should be made of Giovanni Battista Cambieri, Nikola Selak and Bozo Pericic. They all treated the affected patients and described syphilis and 'Scherlievo disease'in Croatian as well as in other languages. Syphilis was present in Dalmatia towns during the 15(th)-20(th) century, remaining a challenge and arousing the interest of current dermatovenereologists as well as other specialists.

Effect of progesterone and pregnancy on the development of varicose veins.

The aim of this study was to investigate the contribution of progesterone in the development of primary varicose veins on lower limbs during pregnancy. In 50 primiparae with varicose veins, serum progesterone level was quantitatively determined in the 14th week of pregnancy and results were compared with those obtained in a control group of 25 primiparae without visible varicose veins. The mean serum progesterone concentration recorded in pregnant women with dilated veins (159.9+/-15.8 nmol/L) was significantly higher as compared with the control group (159.9+/-15.8 nmol/L vs. 40.4+/-1.6 nmol/L; P<0.0001). These findings supported the role of hormonal factor in the development of varicose veins in women.

History of venereology in Croatia.

The term sexually transmitted infections has a wider meaning than the older venereal diseases. It is known that gonorrhea was present even in ancient times, whereas syphilis appeared in Europe at the end of the 15(th) century. Soon cases were observed along the coast in Zadar, Dubrovnik and Istria, and were treated by surgeons. The relatively late establishment of medical schools, along with wars and different governments, were some of the reasons why dermatovenereology as a specialty developed later in Croatia than in other European countries. Nevertheless, during the 19(th) century, many Croatian physicians and dermatovenereologists of the past century were interested in venereology. Among the most important personalities that worked at departments and dispensaries for venereal diseases were Cambieri, Kogoj, Bozic, Nonveiller, Orhel, and many others. They introduced new diagnostic technologies and treatments, and wrote about these diseases. Significant progress was achieved in larger towns where medical schools had been opened. Croatian venereologists also organized several international congresses on sexually transmitted diseases and became members of the respective international societies. Nowadays, the interest of dermatovenereologists has been shifting towards chlamydial infections, herpes genitalis, human papillomavirus genital infection and human immunodeficiency virus infection, and their presence among homosexuals.

The distinction between lesional and non-lesional skin in psoriasis vulgaris through expression of adhesion molecules ICAM-1 and VCAM-1.

Psoriasis vulgaris [pv] is a systemic inflammatory skin disease affecting 2-4% population. It is well known that pv affects some parts of the skin and also whole skin as in erythrodermic form. We still do not know why in pv some parts of the skin are affected and others are not. In our hypothesis we assumed that the whole skin is in <> position and non-lesional skin could become in every moment lesional. According to our hypothesis and also other author's research, high expression of adhesion molecules ICAM-1 and VCAM-1 in lesional as well as non-lesional skin in pv, supports this hypothesis, suggesting a significance of these molecules in pathogenesis of pv. Our hypothesis could be proved by immunohistochemical stain of ICAM-1 and VCAM-1 in lesional and non-lesional skin of pv patient in comparison with healthy skin.

Antonio Grossich- on the centenary of his introduction of iodine tincture painting in the preoperative infection control.

The article presents the life and achievements of Doctor Antonio Grossich, the head of the Department of surgery and gynecology of the Civic hospital in Rijeka. He wrote several literary works, but deserves to be remembered for his clinical and experimental work on antiseptic and aseptic procedure. He introduced the method of painting the operative field with 10% iodine tincture at first in traumas, then in general surgery. The method, for its rapidity, efficacy and not expensive had soon a worldwide success. He also participated actively in the political life of Rijeka before and after the World War I.

[Professor Andelko Wolf, MD, PhD. (1922-2007), eminent epidemiologist and dermatovenerologist]. / Prof. Dr. Sc. Andelko Wolf (1922.-2007.), ugledni epidemiolog i dermatovenerolog.

Professor Andelko Wolf graduated medicine from the University of Zagreb School of Medicine in 1947. First he specialised in epidemiology and became head of the Brucellosis Centre in Rijeka for the Istria region. Later he also specialised in dermatovenerology at the Department for Skin and Venereal diseases in Rijeka. He passed the specialty board exam in dermatovenerology in 1958 and became teaching assistant. In 1973, he became assistant professor and in 1981 full professor. At the Department he founded the Laboratory for Mycology and allergology. Later he focused on occupational skin diseases and photodermatology. His doctoral thesis was on the action of light on the skin. He chaired the Clinic and was a member of various Hospital and Medical School committees. He was an excellent clinician undergraduate and graduate student teacher in Rijeka and Zagreb. He published around eighty papers on dermatology, but also on the necessity to reform medical studies.

Giovanni Battista Cambieri and the beginning of venereology in Rijeka region.

In 1790, an infectious disease appeared in the village of Skrljevo near Rijeka, and spread to the nearby villages and then to Istria, Slovenia and other parts of Croatia. In 1800, the nature of the disease was first investigated by the protomedicus Massich, who believed it was a combination of syphilis and scabies. After him, the protomedicus of the region G. B. Cambieri, who graduated in Pavia and came to Rijeka in 1797, studied the illness, gave a description of the disease and believed it was a morbus sui generis, and termed it morbus of Scherlievo. He was a gifted physician, used all his knowledge, skills and organization capabilities to arrest the disease, and published his works in Italian journals (in 1812 and 1819). Cambieri studied the disease in thousands of patients in local hospitals, and took the initiative to open a new Civic Hospital with a department of syphilidology. He divided the disease into four stages and with permission of the authorities he tried different therapies. With time, he found the disease to be a form of syphilis and treated it with mercury compounds. After his death in 1838, he left his money to the Hospital of Holy Spirit in Rijeka (Cambieri Foundation), which permitted its development.

Molecular and genetic mechanisms in melanoma.

Recent studies have indicated an increasing incidence of melanoma worldwide. Although UV signature mutations are found rarely in melanoma cells, there is some evidence that intense intermittent exposure to sunlight can induce melanocyte tumorigenesis, and this is also observed after UV irradiation in some animals. The purpose of this paper is to review some of the most important mechanisms involved in the pathogenesis of this tumor. Genetic studies showed the familiar melanoma is linked to the mutation or deletion of the suppressor gene CDKN2A, and perhaps to CDK4. Studies showed that BRAF mutation is frequent in primary and metastatic melanoma cells but also in naevocytic nevi. This mutation activates the RAF/MEK pathway. Exposure to UV radiation induces immunosuppression. Recent investigations showed that chemokines, angiogenesis, metalloproteinases can play a role in the mechanism of metastasis. In spite of these advances the initiating events are still not completely understood. In conclusion, the pathogenesis of melanoma is very complex because numerous genetic and epigenetic factors are implicated in its development and progression, but some of the showed mechanisms can be targets for new therapies.

Phytophotodermatitis in Rijeka region, Croatia.

Contact with plants can cause phototoxic or rarely photoallergic reactions. Phototoxic dermatitis (photophytodermatitis) occurs after contact or ingestion of plants containing furocumarins i.e. psoralens and followed by sun exposure. Skin lesions develop usually after 24-48 hours with erythema, bulla formation, itch or pain, followed by a long lasting hyperpigmentation. Furocumarins can be linear i.e. psoralens (5-MOP, 8-MOP), or angular like angelicin and pimpinellin. Their binding to DNA causes cellular damage. This can happen in florists, gardeners, farmers, horticulturists, food handlers, and botanists. The plants causing phototoxic reaction can vary with the local flora but are commonly a member of the family apiaceae (formerly umbelliferae), family rutaceae, leguminosae and moraceae. The authors give special consideration to the phytophotodermatitis that appeared in their region in spring and summer during a three year period.

Correlation between clinical-dermatoscopic and histopathologic diagnosis of skin tumors in our patients.

In this study 103 patients with skin tumors were examined. Among them there were 43 (42%) male patients and 60 (58%) female patients. Working diagnosis was obtained by clinical examination using dermoscope. After excision of lesion, working diagnosis was compared to pathohistological diagnosis. In our study we used dermoscope Heine proper delta 10. The clinical-dermoscopic diagnosis included verrucae seborrhoicae in 26 (25.24%), fibropapilloma in 17(16.5%), naevus pigmentosus in 9 (8.79%), naevus dysplasticus in 4 (3.88%), fibroma molle in 8 (7.76%), Mb. Bowen in 1 (0.97%), basal cell carcinoma in 7 (6.79%), squamous cell carcinoma in 6 (5.82%), haemangiofibroma in 1 (0.97%), haemangioma in 3 (2.91%), keratosis actinica in 5 (4.85%), melanoma malignum in 6 (5.82%), naevus fibromatosus in 2 (1.94%) cases and naevus blue in 1 (0.97%), naevus traumatisatus in 1 (0.97%), verruca vulgaris in 1 (0.97%), lymphocytoma in 1 (0.97%), naevus verrucosus in 1 (0.97%), lentigo solaris in 2 (1.94%) and Reed nevus in 1 (0.97%) case. Dermoscopic diagnosis were conformable with pathohistological diagnosis in 75 cases (72.82%). We presumed that dermatoscoping obtains correct diagnosis of skin tumors.

A dose-finding study of azithromycin in the treatment of acne vulgaris.

This open, multicenter, comparative, randomized study included 120 subjects with papulopustular stage of acne vulgaris. Subjects were randomized to one of the three treatment groups (A, total dose 4.5 g of azithromycin in 7 weeks; B, total dose 6.0 g in 10 weeks; and C, total dose 7.5 g in 13 weeks). The aim was to identify the optimum azithromycin dose in the treatment of acne vulgaris through monitoring the efficacy and safety of three dosage regimens. Clinical efficacy was assessed upon completion of study therapy and six months of therapy initiation. Post-therapeutic efficacy assessment was available in 104 subjects. The difference between three treatment groups was most pronounced in the "cure" category (36.11% in group A, 58.82% in group B and 55.88% in group C) and "failure" category (8.33% in group A, and no failures in groups B and C). Follow up efficacy assessment was available in 87 subjects. The group percentage of "cure" was lower and group percentage of "treatment failure" higher in group A than in groups B and C. Azithromycin in a total dose of 6.0 g in 10 weeks seems to be a promising agent in the treatment of papulopustular acne vulgaris with few side effects and good patient compliance.

Occupational skin diseases caused by UV radiation.

This overview highlights the risk of skin diseases arising in workers exposed to ultraviolet radiation (UVR) at their workplace. There is a plethora of skin manifestations in outdoor workers such as seamen, fishermen, farmers after acute intense or long-term exposure to solar UVR, but some cutaneous diseases may also develop in indoor workers exposed to artificial sources. In recent years, investigations of the biological effects and damage caused by UVB and UVA on the skin have improved our understanding of the cellular and molecular mechanisms of photoaging, skin cancer and other skin diseases caused by UVR exposure. The necessity of primary prevention in workers exposed to UVR is emphasized.

Occupational skin diseases caused by solar radiation.

UV radiation is present in sunlight and can be emitted from numerous artificial sources. Outdoor workers are exposed to sunlight in a wide variety of occupations like sailors, fishers, construction workers, farmers, and other. Presented are the skin diseases caused by sunlight exposure. They may be of little medical importance such as stigmata or create problems like photoaging, skin carcinoma, melanoma, phototoxic and photoallergic reactions. Shown are briefly data on skin cancer in the Rijeka region in outdoor occupations, the legislation and necessity for prevention. Psoriatic patients need particular caution because they are exposed to UVR, tars, and immunosuppressive drugs during the treatment.

Epidermal malignant tumors: pathogenesis, influence of UV light and apoptosis.

Basal cell carcinoma and squamous cell carcinoma, collectively termed non-melanoma skin cancers are the most common malignant tumors in humans. Basal cell carcinoma grows slowly and metastatic spread is very rare. Squamous cell carcinoma is characterized by infiltrative, destructive growth and metastasis. Long-term exposure of skin to UV light has a great impact on development of these epidermal malignancies. UV light induces cascade of events like well known DNA damage of keratinocytes as well as still completely undetermined influence on apoptotic process through expression of proapoptotic and antiapoptotic molecules. The major role in development of skin cancer is given to proapoptotic p53 molecule or tumor suppressor gene which mutation due to UV exposure leads to resistance of DNA-damaged cell to apoptosis. Other proapoptotic molecules such as Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are strongly expressed in basal cell carcinoma and squamous cell carcinoma that could be explained by the ability of tumor to escape the attack of immune system.

Photocarcinogenesis--molecular mechanisms.

The carcinogenicity (photocarcinogenicity) of sunlight to human skin has been recognized more than a century ago. Last decades numerous experimental studies show that UV rays damage DNA, cause gene mutations leading to the development of malignant tumors such basal cell carcinomas, squamous cell carcinomas and melanomas. The tumors occur most frequently in fair skinned people, and the mutations typically are found at dipyrimidine sites with C-T or / and CC-TT tandem double mutations. The authors briefly summarize their investigation of the p53 suppressor gene, and expose their hypothesis of hTERT involvement in cancerogenesis. Also their underline the importance of UV induced immunosuppression in photocarcinogenesis. Psoriatic patients are exposed to numerous cancerogens in their treatment. A better understanding of the mechanisms of photocarcinogenesis could provide new ways in the treatment of skin tumors.