Veljko Maric, Milan Jovanovic, Natasa Zdravkovic, Marina Jovanovic, Nevena Gajovic, Milena Jurisevic, Marina Jovanovic and Ivan Jovanovic
Colorectal cancer (CRC) represents one of the most common cancers. It is frequently diagnosed at advanced stages, indicating on need for new diagnostic markers. Th e aim of this study was to determine systemic and fecal values of IL- 17 and IL-33 in patients with CRC and the relationship with clinicopathological aspects of disease. Th e blood samples and feces liquid fraction of 50 patients with CRC were analyzed. Serum and fecal levels of IL-33 and IL-17 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Fecal levels of IL-33 and IL-17 were increased in CRC patients with poor tumor tissue diff erentiation. Serum IL-33 and fecal IL-17 were increased in patients with presence of lung/liver metastasis or peritoneal carcinomatosis, respectively, while enhanced fecal IL-33 was detected only in patients with peritoneal carcinomatosis. Positive correlation between IL-33 and IL-17 values in sera and feces, respectively was also observed. We believe that increased local values of IL-33 and IL-17, reflected trough higher fecal concentration, in CRC patients with poor tumor tissue differentiation and with presence of lung/liver metastasis or peritoneal carcinomatosis may be considered as a sign of the tumor’s malignant progression and, consequently, of a poor prognosis for patients.
Mirjana Đukić, Milica Ninković and Marina Jovanović
Oxidative Stress - Clinical Diagnostic Significance
Elevated free radical production and/or insufficient antioxidative defense results in cellular oxidant stress responses. Sustained and/or intense oxidative insults can overcome cell defenses resulting in accumulated damage to macromolecules, leading to loss of cell function, membrane damage, and ultimately to cell death. Oxidative stress (OS) can result from conditions including excessive physical stress, exposure to environmental pollution and xenobiotics, and smoking. Oxidative stress, as a pathophysiological mechanism, has been linked to numerous pathologies, poisonings, and the ageing process. Reactive oxygen species and reactive nitrogen species, endogenously or exogenously produced, can readily attack all classes of macromolecules (proteins, DNA, unsaturated fatty acid). The disrupted oxidative-reductive milieu proceeds via lipid peroxidation, altered antioxidative enzyme activities and depletion of non-enzymatic endogenous antioxidants, several of which can de detected in the pre-symptomatic phase of many diseases. Therefore, they could represent markers of altered metabolic and physiological homeostasis. Accordingly, from the point of view of routine clinical-diagnostic practice, it would be valuable to routinely analyze OS status parameters to earlier recognize potential disease states and provide the basis for preventative advance treatment with appropriate medicines.
Genital herpes is a chronic, nearly always active herpes simplex virus (HSV) infection of sacral ganglia, that may appear bilaterally and in more ganglia than previously thought. It represents one of the most prevalent sexually transmitted infections, and the most frequent cause of genital ulcer disease in the general populations of developed countries. It is caused by HSV type-2 (HSV-2) in 60-80% of cases, with HSV-1 infections causing the remainder. Genital herpes caused by HSV-1 is on the rise. Since genital HSV-1 infections have higher risk for transmission from mother to infant during delivery than HSV-2, they account for 30% of all cases of neonatal herpes. Serological studies have found prevalence of HSV-2 in the general population of developed contries to be up to 25%. Thirty years ago, herpes was defined as “Today’s Scarlet Letter”in the absence of reliable serological tests and highly effective medications, for diagnosis and treatment of genital herpes. In 2000, apart from virus isolation in cell culture (70% sensitivity), that has long been regarded as the diagnostic gold standard, type specific serological tests and higly effective antiviral agents have evolved. However, the following questions were raised: should serological testing be routinely recommended in asymptomatic patients; can antiviral therapy reduce asymptomatic shedding of the virus; can antiviral therapy reduce sexual transmission of infection; can antiviral therapy reduce acquisitation of viral copathogens, such as human immunodeficiency virus (HIV)? Now, ten years later, we know the answers. Type specific HSV DNA detection by real-time PCR assays (100% sensitivity) are tests of choice for every person with recurrent genital ulcers lasting more than 4 days, and must be available in those laboratories currently performing a significant number of PCR tests for different purposes. Type specific IgG serology assays are indicated in all asymptomatic persons who are at increased risk for HSV infection. In sexually active patients experiencing ≥ 6 recurrences per year, daily supressive dose of acyclovir, valacyclovir or famciclovir should be discontinued after a maximum of a year of continuous antiviral therapy in order to reassess recurrence frequency. If necessary, the therapy should be restarted after at least two recurrences. With such expansive diagnostic possibilities and more aggressive therapeutic approaches, we can define genital herpes not as a “Scarlet Letter”, but as a “widespread untoward consequence of human sexuality”.
Slobodan Stojanović, Nada Vučković, Marina Jovanović and Kosta Petrović
The authors present a rare case of congenital pachydermoperiostosis associated with striate palmoplantar keratoderma in a 55-year-old female. Pachydermoperiostosis (PDP) is a heterogeneous syndrome characterized by hypertrophic changes involving predominantly the skin and bones of the extremities: pachydermia, clubbing of the fingers and toes, and hypertrophic osteoarthropathy. Primary pachydermoperiostosis (Touraine-Solente-Gole syndrome) (PPDP) or primary hypertrophic osteoarthropathy (PHO) is a rare congenital disorder and is one of two types of hypertrophic osteoarthropathy. In addition to the three main criteria, which are confirmed clinically, histologically, and by X-ray, there may be other additional clinical features. Hyperhidrosis of the hands and feet may be troublesome. The skin of the face, forehead and scalp becomes grossly thickened and thrown into folds. The folding of the scalp produces a form of cutis verticis gyrata. Additional clinical features include hypohidrosis, seborrhea, sebaceous gland hyperplasia and folliculitis, carpal and tarsal tunnel syndrome, chronic leg ulcers and calcification in the Achilles tendon. Our patient presented with most of these additional clinical features, such as acro-osteolysis of the fingers and toes, which generally occurs occasionally. In regard to palmoplantar keratoderma, we have not found reports of its association with PPDP in the available literature.
Unlike PPDP, secondary pachydermoperiostosis (secondary hypertrophic osteoarthropathy -SHO) occurs in association with severe pulmonary disease such as bronchiectasis, abscess, bronchial carcinoma, pleural mesothelioma, or thymic, esophageal or stomach cancer, which were all excluded in our patient.
In conclusion, this paper presents a congenital form of pachydermoperiostosis in a female also suffering from striate keratoderma. According to the available literature, this is the first case report of comorbidity between these two dermatoses.
Bosiljka M. Lalević-Vasić and Marina Jovanović
The seven years’ war (1912 - 1918) and epidemics of infectious diseases, led to a great loss of lives and medical corps of Serbia. As already stated, venereal and skin diseases were spreading in the postwar period that can be seen from medical reports of dermatovenereology institutions. They contain appropriate pathologies and some specific conditions under which they developed. In dermatovenereal pathology, venereal diseases were still dominating. In the outpatient Clinic for Skin and Venereal Diseases, 10.000 patients were examined during the period from 1919 to 1921, venereal diseases accounted for 73.13%, whereas skin diseases accounted for 26.87% of all established diagnoses. A similar distribution existed at the territory of Serbia (Belgrade excluded) in 1931: venereal diseases accounted for 73.4%, and skin diseases for 26.6%; moreover, in Belgrade, the situation was even more drastic: venereal diseases accounted for 84.7%, and skin diseases for 15.3%. However, in the student population, the distribution was reversed: 43% and 57%, respectively. In regard to venereal diseases, in the series from 1919 to 1921, non-endemic syphilis was the most common disease, if serologically positive cases (latent syphilis) were added up to the clinically manifested cases. In the same series of patients, syphilis was staged as follows: syphilis I in 10%, syphilis II in 29.3%, syphilis III in 1.7%, tabes dorsalis in 0.8%, and latent syphilis in 56% of patients. In regions with endemic syphilis, from 1921 to 1925, the distribution was as follows: syphilis I in 4%, syphilis II in 49.8%, syphilis III in 18.3%, hereditary syphilis in 1.3%, and latent syphilis in 26.5% of patients. In patients suffering from gonorrhea, balanitis was found in 4.5%, and arthritis in 0.43% of cases. Generally, spreading of prostitution had a significant role, and its abolition was an important preventive action. In regard to skin diseases, in the above-mentioned series of patients, treated at the Outpatient Clinic for Skin and Venereal Diseases (1919 - 1921), scabies was the commonest skin disease (26.7%), eczemas were the second most common (21.8%), followed by pyococcal diseases (20.4%), while fungal diseases (4.5%) and skin tuberculosis (1.9%) were considerably less frequent.
This is the final report about the foundation of modern dermatovenereology in Serbia.
Đorđije Karadaglić and Marina Jovanović
Actinic keratosis is an intraepidermal proliferation of transformed, atypical keratinocytes, induced by exposure to solar ultraviolet radiation. Many authors believe that it is the earliest form of squamous cell carcinoma. More than 40% of all metastatic squamous cell carcinomas develop from actinic keratosis. The clinical, histological and molecular characteristics of actinic keratosis are those of squamous cell carcinomas. Since it can be extremely hard to distinguish actinic keratosis from some squamous cell carcinomas, treatment can be rather difficult. The best treatment of actinic keratosis is its prevention. The main reason for therapy which is universally accepted, is prevention of squamous cell carcinoma. A number of options are available, but when considering the efficacy, invasive procedures remain the standard treatment. Treatment of individual lesions may prevent further progression of actinic damage present in the surrounding skin
Slobodan Stojanović, Nada Vučković and Marina Jovanović
Ulerythema ophryogenes and keratosis follicularis spinulosa decalvans are rare folliculocentric keratotic disorders, from the group of follicular genokeratoses, characterized by keratosis pilaris atrophicans: follicular keratotic papules, sometimes with surrounding erythema, which eventually result in fibrosis, atrophy, progressive scarring and permanent hair loss. Ulerythema ophryogenes begins at birth or soon thereafter; it involves the lateral eyebrows, spreads medially and eventually affects the entire eyebrows, cheeks, and less frequently, forehead and asjecebt scalp. Involvement of the scalp has apparently not been reported in cases in which the eyebrows were predominantly involved. In addition to sporadic cases, ulerythema ophryogenes has been reported among relatives. Keratosis follicularis spinulosa decalvans is also a genetically heterogeneous syndrome which begins in infancy or childhood by involving hair bearing skin, especially the scalp; rarely it is confined to the face involving only eyebrows and eyelashes, but affects predominantly the scalp, leading to severe progressive cicatricial alopecia. Both conditions tend to progress until puberty.
The authors present a case of an otherwise healthy 19-year-old male patient, with absence of lateral eyebrows since childhood, which spread symmetrically and medially, until puberty affecting the entire eyebrows, whereas the eyelashes were completely spared. On examination, skin findings on the face, trunk and extremities pointed to ulerythema ophryogenes: apart from hair loss, the lateral eyebrows were highly erythematous; a great number of disseminated follicular, slightly keratotic papules (keratosis pilaris) pin- or match-head sized, were seen on the trunk, extensor surface of the arms and legs, as well as the buttock, and on palpation the skin felt like a “nutmeg grater”. However, follicle-based erythematous papules (focal patchy alopecia) were found not only along the eyebrows but also partly in the parietal capillitium forming focal patchy alopecia, which is a finding characteristic for keratosis follicularis spinulosa decalvans; the histopathological analysis of the biopsy specimens taken from the parietal capillitium has confirmed the clinical diagnosis.
Cytogenetic analysis showed no karyotypic abnormalities. Family history showed that the patient’s mother and maternal grandfather also suffered from hair loss especially of the lateral eyebrows.
This paper presents an overlap between two rare follicular genokeratoses in a young male with a positive family history, who presented with ulerythema ophryogenes involving not only the eyebrows, but also the scalp, in the form of parietal, focal cicatricial patchy alopecia.
Bosiljka M. Lalević-Vasić and Marina Jovanović
After the First World War, Serbia was facing the lack of hospitals and physicians, and organization of the health care system was a real challenge. Both problems were closely associated with dermatovenereology. Between the two world wars, a great contribution to the development of Serbian dermatovenereology as a current discipline was given by Prof. Dr. Đorđe Đorđević, who was the first director of the Clinic for Skin and Venereal Diseases in Belgrade (1922 - 1935), and by his closest associate Prof. Dr. Milan Kićevac (1892 - 1940) who was his successor at the position of the director of the Clinic (1935 - 1940). In 1922, Prof. Dr. Đorđe Đorđević was the founder of two institutions significant for Serbian dermatovenereology: Clinic for Skin and Venereal Diseases, where he also acted as a director, and the Department of Dermatovenereology at the School of Medicine in Belgrade, where he was the first teacher of dermatovenereology. In 1927, Prof. Dr. Đorđe Đorđević initiated the foundation of the Dermatovenereology Section of the Serbian Medical Society, and he and his associate and successor, Prof. Dr. Milan Kićevac were the main organizers of the Association of Dermatovenereologists of Yugoslavia. With this Association, all other regional dermatovenereology sections in the County became parts of the Pan-Slavic Dermatovenereology Association. Prof. Dr. Đorđe Đorđević and Prof. Dr. Milan Kićevac also organized the First, Second and the Third Yugoslav Dermatovenereology Congresses (1927, 1928, and 1929), and in 1931, the Second Congress of Pan-Slavic Dermatovenereology Association. Their teamwork resulted in legislation concerned with health care, eradication of venereal diseases and prostitution, and finally with setting the foundation for professional and scientific dermatovenereology in Serbia. Prof. Đ. Đorđević investigated current problems of venereal diseases and organized professional expeditions in Serbia and Montenegro studying the expansion of syphilis. However, in his experimental work, Prof. M. Kićevac investigated photo-dermatoses and the IV venereal disease, at the same time pointing to immunological phenomena in streptococcal and staphylococcal infections. Dr. Vojislav Mihailović (1879 - 1949) was a significant figure in Serbian dermatovenereology and acted as the Chief of the Department of Skin and Venereal Diseases within the General Public Hospital in Belgrade. His scientific papers and books on the history of dermatovenereology and general medicine had a great impact on the Serbian dermatovenereology. His books dealing with the history of dermatovenereology: “The History of Venereal Diseases till 1912” and “Out of the History of Sanitary Health Care in the Rebuilt Serbia from 1804 - 1860”. Associate Professor Dr. Sava Bugarski (1897 - 1945), a student of Prof. Dr. Kićevac and later the director of Clinic for Skin and Venereal Diseases in Belgrade (1940 - 1945), was engaged in the field of experimental dermatovenereology. Dr. Jovan Nenadović (1875 - 1952), one of the most eminent physicians in Novi Sad, took part in the foundation and work of the Dermatovenereology Section of the Serbian Medical Society as well as its honorary life president. In 1919, he founded the Dermatovenereology Department within the Novi Sad Hospital, as well as an Outpatient Dermatovenereology Clinic, outside the Hospital, although he was the director of both institutions. In the period between the two world wars, among the most prominent physicians of the Military Sanitary Headquarters who contributed the development of dermatovenereology were the chiefs of the Dermatovenereology Department of the General Military Hospital in Belgrade: Major, later on, Brigadier General, Dr. Božidar Janković (1874 - 1936), and the Sanitary Brigadier General, Dr. Milivoje Pantić (1885 - 1959). Dr. B. Janković wrote important professional papers, among which the following are most significant: ”Fight against Venereal Diseases in the Army” and ”Treatment of Syphilis with Silber-Salvarsan.” Distinguished physicians of the military sanitary service, such as Dr. Petar Davidović, made significant contributions to the work of civilian dermatovenereology institutions of that time. In 1921, Dr. Petar Davidović was the director of the newly founded Venereal Department of the Niš Public Hospital, which was on a high professional level.
Bosiljka M. Lalević-Vasić and Marina Jovanović
After the First World War, Serbia was ravaged and in ruins, whereas the Health Care Service was destroyed. Organization and reorganization of the Health Care Service started with a fight against the spread of infectious diseases. Foundation of specialized health institutions was among the first tasks. As early as 1920, an Outpatient Service for Skin and Venereal Diseases was established and managed by Prof. Đorđe Đorđević. In 1922, after he was appointed as Associate Professor at the newly established Faculty of Medicine in Belgrade, he founded a Clinic for Skin and Venereal Diseases, and acted as its first director. In 1928, a Municipal Outpatient Clinic for Skin and Venereal Diseases was founded, whereas in 1938 a modern organization of the Service was established in a new building. After a break during the I World War, the Dermatovenereology Department of the General Military Hospital in Belgrade, founded in 1909, continued working until the Second World War. In Novi Sad, the City Hospital was founded in 1909, including a Dermatovenereology Department. After the First World War, in 1921, Dr. Jovan Nenadović founded a Department of Skin and Venereal Diseases (100 beds) in the General Public Hospital, as well as, an independent Public Outpatient Clinic for free-of-charge treatment of patients with venereal diseases. In Niš, the first Organization Unit for Venereal Diseases was founded in 1912, but the Department of Venereal Diseases was founded in 1921, and it was managed by Dr. Petar Davidović, while in 1927 a Department of Skin and Venereal Diseases was established within the General Public Hospital. In 1920, a Dermatovenereology Department of the Military Hospital in Niš was established. Apart from these, as early as 1921, there was a total of 7 Outpatient Clinics in Serbia, and in 1923 there were 14 venereal departments, and 1 dermatovenereology department.