Modern approach to topical treatment of aging skin.

The main processes involved in skin aging are intrinsic and extrinsic. Apart from them, so called stochastic aging connotes cell damage caused by metabolic processes, free radicals and cosmic irradiation. The clinical expression of intrinsic aging include smooth, dry, and thinned skin with accentuated expression lines. It is inevitable and time dependent. Extrinsically aged skin shows signs of photodamage which include appearance of wrinkles, pigmented lesions, actinic keratoses and patchy hypopigmentations. Therapeutic modalities imply photoprotection with sunscreens that prevent sunburns and block ultraviolet irradiation. Other modalities include use of retinoids which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of network antioxidants, such as vitamin E and C, coenzyme Q10, alpha-lipoic acid and glutathione, enhance antiaging effect. The other antioxidants such as green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol, have also antiaging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial and/or medium depth or deep peeling agents for photodamaged skin treatment. Indications for type of chemical peels according to various clinical diagnosis are done, as well as advantages and disadvantages of different types of chemical peels.

New paradigm in training of undergraduate clinical skills: the NEPTUNE-CS project at the Split University School of Medicine.

Clinical skills' training is arguably the weakest point in medical schools' curriculum. This study briefly describes how we at the Split University School of Medicine cope with this problem. We consider that, over the last decades, a considerable advancement in teaching methodologies, tools, and assessment of students has been made. However, there are many unresolved issues, most notably: (i) the institutional value system, impeding the motivation of the teaching staff; (ii) lack of a strong mentoring system; (iii) organization, timing, and placement of training in the curriculum; (iv) lack of publications pertinent to training; and (v) unwillingness of patients to participate in student training. To improve the existing training models we suggest increased institutional awareness of obstacles, as well as willingness to develop mechanisms for increasing the motivation of faculty. It is necessary to introduce changes in the structure and timing of training and to complement it with a catalog, practicum, and portfolio of clinical skills. At Split University School of Medicine, we developed a new paradigm aimed to improve the teaching of clinical skills called "Neptune-CSS," which stands for New Paradigm in Training of Undergraduate Clinical Skills in Split.

The incidence of basal cell carcinoma in Croatia: an epidemiological study.

The aim of the study was to investigate the basal cell carcinoma (BCC) incidence in Croatia in the 2003-2005 period. Data were collected from University Department of Dermatology and Venereology, Zagreb University Hospital Center and National Cancer Registry. The age-specific incidence rate and age-standardized incidence rate were calculated per 100,000 inhabitants according to the latest population census in Croatia from 2001. In the study period, there were 7,244 BCC cases (3,519 men and 3,725 women) in Croatia. The crude incidence rate for the Croatian population of 100,000 was 54.9 for men and 53.9 for women. The age-standardized incidence rate (adjusted for the world standard population) was 33.6 for men and 24.5 for women. The head and neck were almost exclusive localizations of BCC. The highest BCC incidence was recorded in Zadar County. The incidence of BCC was high in both littoral and inland counties of Croatia. Study results will serve as reference figures on studying the trend of BCC incidence in Croatia and Europe in the forthcoming years.

Allergic contact dermatitis to antibacterial agents.

Topical antibiotics are frequently introduced in therapy by various specialists, e.g., dermatologists-venereologists, ENT specialists, proctologists, ophthalmologists, and others. In dermatology, topical antibiotics are used in the treatment of superficial inflammatory skin lesions, acne and rosacea. These agents are also used in the prevention of inflammatory lesions after surgical and corrective procedures. Long-term and uncontrolled application of topical antibiotics, on the skin with impaired protective barrier in particular, implies a risk for the development of hypersensitivity to these agents. Considering the very wide utilization of these agents, hypersensitivity to topical antibiotics poses a major problem worldwide. The groups at a high risk of contact sensitivity to topical antibiotics include patients with chronic venous insufficiency, chronic ulcers and chronic otitis externa, as well as individuals at occupational exposure to antibiotics, e.g., human medicine and veterinary medicine professionals, pharmaceutical industry workers, cattle breeders, etc. When long-term therapy fails to result in improvement in the above mentioned chronic states, the possibility of allergic reactions to topical agents should be taken in consideration. Cross-sensitivity, which is frequently associated with the use of topical aminoglycoside antibiotics, poses a significant problem.

An overview of Bcl-2 expression in histopathological variants of basal cell carcinoma, squamous cell carcinoma, actinic keratosis and seborrheic keratosis.

The Bcl-2 protein has been shown to suppress cell death and protects cell against apoptosis induced by different death-inducing signals. In this study the authors have analyzed imunohistochemically the expression of Bcl-2 protein in the histopathological variants of the most common malignant tumors of the skin--basal cell carcinoma (BCC) and squamous cell tumor (SCC), as well as in the precancerous lesion actinic keratosis (AK) and in benign tumor seborrheic keratosis (SK). Bcl-2 expression in solid, adenoid and cystic variants of BCC exhibited immunoreactivity of tumor stroma with more intense staining among peripheral palisading cells. Morphoeic variant demonstrated reduced amount of Bcl-2 expression. Among SCC in all samples, tumor tissue lack to express Bcl-2 positivity. In cases of hypertrophic and atrophic variants of AK, Bcl-2 expression was confined to basal cell layer, as well as in one case of hypertrophic variant in suprabasal cells. In three histological variants of SK expresseion of Bcl-2 protein was in areas of basaloid proliferation, while in areas of squamous differentiation was negative. In clonal variant immunostaining was positive among cells in characteristic "nests" Distribution of Bcl-2 protein expression in solid, adenoid and cystic variant of BCC showed that peripheral proliferating cells are protected against apoptosis what permits tumor growth. In morpheaform variant reduced amount of Bcl-2 expression indicated that this variant of BCC has increased cell proliferation, and in practice shows tendency for recurrence and difficulties to eradicate. Bcl-2 expression supports the observation that tumor cells are derived from basal keratinocytes. In SCC, lack of Bcl-2 expression indicates that origin of tumor cells is from more differentiated suprabasal keratinocytes. In AK results suggest that immunoreactivity is regulated with respect of the keratinocyte's differentiation status, but not closely correlate with proliferative rate.

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.

Buschke's scleredema and concomitant diseases: report of five cases and literature review.

Scleredema adultorum or Buschke's scleredema is a rare disorder that belongs to the group of mucinoses. Diffuse, sudden swelling, hardening and induration of the skin can occur in children and younger women as well as in older men. The dermis is thickened because of the increased collagen glycosylation, like that in diabetic stiff skin syndrome. The face is most often involved. In older persons the trunk is usually first involved. There is relative sparing of the extremities, with no distal or Raynaud's phenomenon. Eosinophilic fasciitis, scleromyxedema, associated gammopathy, and other forms of edema and mucin deposition must be excluded on differential diagnosis. Antibiotics, sometimes high doses of intravenous penicillin, systemic corticosteroids, systemic PUVA and PUVA bath therapy seem most promising for the management of the disorder. Our patients were aged 27, 60, 64, 69 and 72 years, with typical skin lesions, thus that term "adultorum" does not appear to fit well.

Angiosarcoma arising in sclerodermatous skin.

We report a case of cutaneous angiosarcoma in a 77-year-old female patient with systemic sclerosis. The tumor developed around a large telangiectasia in the left temporal region. Later on, extensive asymptomatic redness and edema with several nodules over the whole left side of the face developed. Since the conservative therapy failed to produce any improvement, a diagnostic skin biopsy was performed. The pathohistological diagnosis was moderately differentiated angiosarcoma. The patient was treated with a combination of chemotherapy and electron beam irradiation. Despite a notable cutaneous improvement, the control check-up revealed the presence of metastases of the lung and liver. This is the first report of cutaneous angiosarcoma occurring in sclerodermatous skin. The possible pathogenesis of this rare tumorogenic transformation of soft tissues is discussed.

A child with Bartonella henselae osteomyelitis of the right humerus.

We present a case of a 22-month-old child with swollen upper part of the right arm and osteolytic lesion of the right humerus, which resembled a neoplastic process. Epidemiological history revealed no scratch marks on the skin or cutaneous papule or pustule. Presumptive diagnosis of hematogenous osteomyelitis was established, but treatment with fusidic acid was unsuccessful. Histological examination of the bioptic specimen of the soft tissue swelling showed a lymph node morphology, with numerous granulomas with central stellate necrosis. Indirect immunofluorescence assay for Bartonella henselae yielded positive results. New treatment included 15 days of trimetoprime and sulfamethoxazole, followed by azithromycin for 5 days. Four months later, swelling resolved and osteolytic lesion almost completely healed with formation of surrounding sclerosis. In conclusion, cat-scratch disease without positive epidemiological history and primary cutaneous papule or pustule may be a serious diagnostic problem, but can be solved by serological and histological examination.

Syphilitic aneurysm: case report.

Tertiary syphilis is a rare, slowly progressive inflammatory disease that becomes clinically visible years after initial infection. Although it can affect any organ in the body, it shows a predilection for the cardiovascular and nervous systems. Today, however, cardiovascular syphilis is a medical curiosity because the disease can successfully be treated with antibiotics in its early phase. We present a case of a 43-year-old male patient with a syphilitic aneurysm of the descendent aorta and our choice of treatment.

Alterations in CDKN2A locus as potential indicator of melanoma predisposition in relatives of non-familial melanoma cases.

AIM: To examine constitutional alterations of CDKN2A/p16INK4A locus as a potential indicator of melanoma predisposition among the first-degree relatives of patients with malignant melanoma. METHOD: The study included eight families with a single member affected with melanoma. Members of the families were screened for allelic cosegregation with 9p21 region polymorphic markers IFNA, D9S126, and D9S104. The patient's tumors were screened for loss of heterozygosity (LOH) with the same markers, as well as for single strand conformational polymorphism (SSCP) variability of CDKN2A. In suspect cases, constitutional DNA was examined by SSCP and direct sequencing. RESULTS: LOH was detected in four cases, and SSCP indicated variability in at least one CDKN2A exon in these tumor samples. In three of four LOH cases, the remaining allele cosegregated within the family, which was interpreted as a preliminary indicator of potential genetic predisposition. In one of these three families, we found constitutional CDKN2A mutations in the patient and one of the relatives. In the second family, only the patient had the constitutionally altered gene, whereas no constitutional CDKN2A alterations were detected in the third family. All significant mutations were different and had not been reported before. CONCLUSION: We detected one case of melanoma predisposition among unaffected family members, which corresponded to statistical expectations for such a small number of screened families. Since constitutional mutations of CDKN2A exons have limited incidence, our stepwise approach seemed to be more informative and more affordable than straightforward CDKN2A sequencing of all subjects.

[Is permanent renal function damage possible after hemorrhagic fever with renal syndrome?]. / Je li moguce trajno ostecenje bubrezne funkcije nakon preboljele hemoragijske vrucice s bubreznim sindromom?

AIM: To investigate the possibility of permanent renal function impairment and other organ lesions following hemorrhagic fever with renal syndrome (HFRS). METHODS: Data on 30/37 patients infected with HFRS, treated at the Department of Infectious Diseases, Split University Hospital, in 1995 were retrospectively analyzed. The data were collected three to six years following the appearance of HFRS. In 1998, 30/37 patients presented for control checkup, when their history data were collected, along with physical examination, hematology and biochemistry tests, and urinalysis. Creatinine clearance and sodium, potassium, chlorine, phosphorus, beta 2-microglobulin and N-acetyl-beta-D glucosaminase in 24-h urine were determined. In native urine, erythrocyturia was observed, with 10 erythrocytes per field were considered pathologic result. During the 1998-2001 period, renal scintigraphy by means of technetium labeled diethylene triaminopentacetic acid (99mTC DTPA) was performed in 13/30 patients. RESULTS: Of subjective discomforts, 29/30 (96.7%) patients reported lumbar pain. Elevated blood pressure was found in 9/30 (30.0%), erythrocyturia in 4/30 (13.3%) and hepatic lesion in 4/30 (13.3%) patients. Decreased creatinine clearance values (< 1.2 ml/s) were found in 4 and increased values (> 2.35 ml/s) in 10 patients. Increased sodium in 24-h urine was recorded in 10/23 and increased beta 2-microglobulin in 6/23 (26%) patients. Proteinuria exceeding 150 mg/day was detected in 11/23 (47.8%) patients. Scintigraphy of the kidneys demonstrated reduced glomerular filtration (< 100 ml/min/1.72 m2) in 3/13 patients. Prolonged mean times (> 5 minutes) of radiopharmaceutical passage through the renal parenchymae were found in 7/13 (53.8%) patients. DISCUSSION: Studies performed in 30 patients three years after they had recovered from HFRS revealed changes suggesting a mild to moderate impairment of the renal function. Hypertension found in 9/30 patients was a significant finding, considering the fact that all subjects were soldiers, thus having undergone through examinations to prove them completely healthy prior to joining army. Hypertension results were consistent with those reported from the USA. Although erythrocyturia points to urinary tract damage, its glomerular or postglomerular origin was not examined. Decreased creatinine clearance found in 4/23 patients suggested functional renal impairment. Increased natriuresis found in 10/23 patients implied tubular damage, i.e. reduced ability of tubular cells for sodium reabsorption from primary urine. Non-selective albuminuria detected in 11/23 patients indicated permanent lesion of the glomerular basal membrane. Increased beta 2-microglobulin found in 6/23 patients indicated that the lysosomal enzyme level was elevated only in the acute stage of the disease, but may have been an indicator of permanent lesion. No description of post-HFRS scintigraphic lesion of the kidneys was found in the literature. A decreased value of glomerular filtration, found in three patients, and especially the prolonged mean time of glomerular micropharmaceutical passage in 7/13 (53.8%) patients may have suggested glomerular damage. However, the possible reason may have also been a reduced passage of glomerular filtrate through the damaged lower parts of the nephrons. Transaminase increase during the acute stage of HFRS suggested the possible liver infection, maybe even hantavirus replication in hepatocytes. Even though biopsy confirmed the histologic picture of chronic hepatitis in one patient, the question remains whether it could have been caused by hantavirus. CONCLUSION: Studies performed in 30 patients with a history of HFRS revealed renal function impairment, along with hypertension and damage to the liver parenchyma in some patients. The results obtained showed that the HFRS infection in Croatia may have entailed chronic sequels. To confirm this hypothesis, additional studies including a control group of hantavirus negative persons are needed.

Health care relief to neighbors: Split University Hospital during the 1991-1995 war in Bosnia and Herzegovina.

AIM: To assess the workload of the Split University Hospital during the war and its role in providing help to the neighboring countries. METHODS: We reviewed all available records of patients admitted to the four (out of 15) departments: General Surgery, Traumatology, Dermatovenerology, and Pulmonology. The files of 37,821 patients (78% of total number) treated during 1990-1995 were analyzed. RESULTS: The workload of the hospital paralleled the political crisis in Bosnia and Herzegovina (BH) -- the number of patients from BH increased more than 10-fold between 1990 and 1993, including during the time of armed conflict between BH Croats and Bosniaks (1993-94). Among them, there were 84% of ethnic Croats and 16% of ethnic Bosniaks. The hospital spent US$6.2 million (18% of total costs) on the treatment of BH citizens. Approximately two thirds of BH citizens (62%) were treated at one of the surgical departments, and approximately one third of Bosniak patients were young males, admitted for treatment of war-related injuries. CONCLUSION: The Split University Hospital took a large burden of managing BH citizens, despite the armed conflict of Bosnian Croats and Bosniaks, indicating the high professionalism of the hospital staff and management. Such attitude can contribute to peace and post-war reconciliation in the region.