The rise in melanoma incidence in Croatia

The incidence of skin cancer, and particularly of cutaneous melanoma, has increased substantially over the recent decades. It has generally been assumed that early diagnosis may in fact be responsible for a part of incidence increase. The aim of the study was to analyze the prevalence and distribution of primary cutaneous melanoma among biopsy specimens during the 1991-2000 period. The Surgical Pathology computerized registry was used to identify patients with primary cutaneous melanoma. The distribution of primary cutaneous melanoma according to Clark showed an increased number of melanoma in situ diagnosed during the 1997-2000 period. It could not be definitely concluded whether these data resulted from more common excision of suspicious pigmented skin lesions or there was an increase in the melanoma rate as a consequence of environmental changes. Fortunately, nowadays new patients with cutaneous melanoma are mostly diagnosed early in the clinical course of disease when it can be successfully managed by simple surgical treatment.     

The concept of neuropsychiatry: a historical overview

The elusive nature of the social practice called neuropsychiatry is the most important obstacle for writing its history. At different times, and in different countries, the term has been used to name different ideological and professional packages. Choosing any of these as the prototype would, however, bias and regionalize the historical account. One solution is to identify an ideological marker or common denominator. To spin its yarn, this paper has chosen the foundational claim (putatively common to all practitioners of 'neuropsychiatry') that all 'mental disorders are disorders of the brain'. Three among its results are worth noting. One is that the meaning and exercise of 'neuropsychiatry' will continue to depend on social, economic and political factors; this augurs future instability. The second is that each time that the foundational claim has been uttered in history it has meant something different. Further research is needed to clarify whether this is due to the way in which the claim becomes 'inscribed' in different cultural niches; what is clear is that by using the foundational claim as a marker it is not possible to establish a continuity in the progress of neuropsychiatry. The third finding is that users of the foundational claim require the use of a concept of matter and in this paper 'plain' and 'baroque' types of matter have been identified. To explain the origin of mind, those using the plain notion need to resort to external ingredients and their narratives incorporate bits of the real world. Users of the baroque definition do not need such aids. It is not for the historian to judge which of these two definitions is more felicitous and more conducive to the moral and aesthetic edification of psychiatry and her patients.     

Age-related seroprevalence study for St. Louis encephalitis in a population from Cordoba,Argentina

A serological screening was performed in 615 individuals aged 0-87 years, living in the city of Cordoba, Argentina to study the relationship between antibody prevalence for the SLE virus and age. A 13.98% prevalence of neutralizing antibodies was obtained and its relation to age was significantly high (p = 0.045). The highest seroprevalence was noted on individuals over 60 years old (>20%), whereas no subject under 10 was seropositive for this virus. Our results confirm that the agent is endemic in this area and neurological pathology studies should be performed on those individuals aged 60 since they represent the most susceptible group to SLE virus.     

Surgical wound infection associated with Staphylococcus sciuri

We describe a case of surgical wound infection due to Staphylococcus sciuri. The isolated strain was susceptible to trimethoprim-sulfamethoxazole, erythromycin, chloramphenicol, ciprofloxacin and vancomycin and resistant to gentamicin, clindamycin, rifampicin, methicillin, ampicillin and ceftriaxone. The multiresistance of the strain had a serious impact on the prolonged course of the infection. Although this bacterium is principally found in animals, our strain was probably of nosocomial origin.     

Characterization and evolution of NS5A quasispecies of hepatitis C virus genotype 1b in patients with different stages of liver disease

The quasispecies nature of hepatitis C virus (HCV) is thought to play a central role in modulating viral functions. Recent work has linked NS5A protein with viral replication, resistance to interferon (IFN), and control of cellular growth, probably through the interaction of its protein kinase R (double stranded RNA-activated protein kinase, PKR) binding domain (PKR-bd) with cellular PKR, but knowledge of how PKR-bd viral population evolves during disease progression is limited. Since we have previously described an association between amino acid composition of the PKR-bd and the presence of HCC, in this report we further investigated the dynamic behavior of viral population parameters by sequencing an average of 20 clones per sample in 27 samples from 19 untreated patients with different degrees of liver disease, 8 of whom were followed over time. Viral population parameters varied widely from patient to patient, but no differences were observed in the complexity, diversity, types of nucleotide changes, or evolutionary pattern of the quasispecies according to the stage of liver disease. In five samples, we detected "quasispecies-tails"; that is, clones whose minimum genetic distance to the remaining clones of their own quasispecies were higher than the maximum genetic distance found between any other two clones of the same sample. In summary, independent of the degree of liver disease, or the mutations detected within the consensus sequence of the PKR-bd, the NS5A of HCV presents a flexible and variable quasispecies structure that remains largely stable during the natural course of an HCV infection, highlighting the central role of NS5A protein in viral life cycle.     

Liposomal daunorubicin (DaunoXome) in multiple myeloma: a modified VAD regimen using short-term infusion

Liposomal daunorubicin replacing conventional anthracyclines may reduce toxicity and enhance efficacy of chemotherapy. In this phase I study, we evaluated liposomal daunorubicin (DaunoXome) in combination with vincristine and dexamethasone for toxicity, pharmacokinetics and potential efficacy in patients with multiple myeloma. The main objective was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of liposomal daunorubicin combined with vincristine and dexamethasone (VLDD). Additionally, pharmacokinetics were determined at higher dose levels. Seventeen multiple myeloma patients were enrolled in this trial; 76% of the patients had relapsed or refractory multiple myeloma. Successive cohorts received liposomal daunorubicin at doses of 40, 60, 80 and 100 mg/m2 on day 1 in combination with vincristine 1.4 mg/m2 (day 1) and oral dexamethasone (40 mg, days 1-4). DLT occurred at 100 mg/m2. Liposomal daunorubicin at 80 mg/m2 was well tolerated in this protocol and should be used for further phase II studies with the VLDD regimen. In this phase I trial, 64% of the patients achieved a partial remission or a minor response.     

The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study

Prior uncontrolled studies of nonsmokers with major depressive disorder (MDD) indicate rapid reduction in depressive symptoms with nicotine patch therapy. This randomized, double-blind, placebo-controlled pilot study examined the effect of nicotine patch therapy on depressive symptoms in non-medicated nonsmokers with current MDD. Due to recruitment difficulties, only 7 were enrolled and of these 6 (5 females, 1 male) completed the study. Participants received either placebo (n = 4) or active (n = 2) patch therapy for 8 days. They completed daily clinic visits during patch therapy and a final visit on Day 12. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HRSD). The mean change in HRSD scores of all participants decreased (p = 0.021) from baseline by Day 1 of patch use. Similar decreases in HRSD scores were observed for placebo and active patch groups. Among the placebo participants, the mean HRSD score decreased (p = 0.038) by Day 2. The study needs replication with a larger sample and utilizing novel recruitment strategies.     

Apoptosis and oxidative stress induced by ochratoxin A in rat kidney

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of fungi. OTA induces a tubular-interstitial nephropathy in humans and in animals. It has been implicated as one of the aetiological agents involved in the development of endemic nephropathy. OTA-induced oxidative stress and apoptosis may play key roles in the development of chronic tubulointerstitial nephritis connected to the long-term exposure to this food contaminant. We studied the effects of low doses of OTA on kidney cells. Wistar rats were treated with 120 g OTA/kg bodyweight daily, for 10, 30 or 60 days. Toxin concentration in kidney was proportional to the time of exposure, and amounted to 547.2, 752.5 and 930.3 ng OTA/g kidney tissue after 10, 30 and 60 days, respectively. OTA treatment caused an increased number of cells undergoing apoptosis in both proximal and distal epithelial kidney cells. The apoptotic cells were visualised using the TUNEL assay and staining with haematoxylin and eosin in situ. The number of apoptotic cells in rats treated for 10, 30 and 60 days increased by 5-, 6.4- and 12.7-fold, respectively, compared with the control cells. However, DNA electrophoresis did not show characteristic fragmentation (DNA laddering). The oxidative stress was evident via increased malondialdehyde formation. The concentration of lipid peroxides showed an increase (36%), but the activity of superoxide dismutase decreased (26%) in 60-day treated rats. In spite of the observed biochemical and morphological changes in the kidney cells, renal functional status was preserved to the end of experiment. This study demonstrates that a combination of morphologic and biochemical markers can be used to monitor early cell death in OTA-induced renal injury. We have shown that the exposure to the relatively low OTA concentrations has activated apoptotic processes and oxidative damage in kidney cells.     

Long and short fiber amosite asbestos alters at a different extent the redox metabolism in human lung epithelial cells

The mechanism by which asbestos fibers are fibrogenic and tumorigenic is still matter of debate. The higher pathogenicity of longer fibers has been traditionally associated with their slower clearance in respiratory airways. However, short amosite fibers, obtained by grinding longer ones, exhibited a lower potential to damage nude DNA and a lower in vitro cytotoxicity. We have thus revisited the two sets of long and short fibers in order to compare their surface properties to their activity in cell systems. In this study we report that, in human lung epithelial cells A549, long amosite fibers, more effectively than the short ones, initiate free radical reactions, inhibit the glucose 6-phosphate dehydrogenase activity and the pentose phosphate pathway, decrease the intracellular level of reduced glutathione, and increase the generation of thiobarbituric acid reactive substances and the leakage of lactate dehydrogenase in the extracellular medium. These results suggest that the shortening of fibers by prolonged milling affects not only their biopersistence, but also their surface properties, hence their interaction with cellular metabolism. Our data provide also a mechanism by which asbestos fibers inhibit the pentose phosphate pathway, i.e., via the oxidative inhibition of glucose 6-phosphate dehydrogenase, which is prevented by reduced glutathione.