Psoriatic arthritis: a retrospective study of 162 patients

AIM: The aim of our study was to determine the prevalence of psoriatic arthritis in the patients with psoriasis and to analyze retrospectively the results of a 34-year multidisciplinary management of the patients with psoriatic arthritis. METHODS: The study included 162 out of 183 treated patients with psoriatic arthritis, aged 48 +/- 15 years. All the patients satisfied the current diagnostic criteria for psoriasis and psoriatic arthritis according to the American College of Rheumatology. RESULTS: Psoriatic arthritis developed in 183 (9.3%) out of 1976 patients with psoriasis. Time interval for establishing the diagnosis was 4 years. A positive family history of the disease had 15.0% of the studied patients. Its onset was most often at 42 years of age in 70.4% of the cases, and 2 months to 59 years after the appearance of psoriasis. Psoriatic arthritis without psoriasis appeared in 1.8% of the patients. A severe form of arthritis had 64.2% of the patients, mainly the patients with scalp psoriasis (chi2 = 3.2; p < 0.05). Nail changes had 35% of the patients. Distal interphalangeal joints were involved in 63.6%, axial skeleton in 36.4%, oligoarthritis in 45.0%, polyarthritis in 55.0%, and mutilating form in 6.8% of the patients. Elevated Erythrocyte Sedimentation Rate was reveald in 61.7% of the patients. Immunoglobulin M (IgM) rheumatoid factor was altered in 4.3% of the patients. The human leukocyte antigen (HLA) typing in the 28 patients were: A2 32.0%, A3 18.0%, Al and A9 14.0%, A28 and A29 3.5%, B8 and B16 14.0%, B5 and B12 11.0%, B13, B15, B18, B27 and B35 7.0%. Radiologic changes were most often in hand and foot joints, less frequently in the knees and quite infrequently in hips and shoulders joints. Sacroiliitis was found in 46.4% of the patients. Psoriasis was treated with topical corticosteroids and salicylic ointments in all the patients, ultraviolet (PUVA therapy) in 5.6% and retinoids in 4.3% of them. Artrithis was treated with nonsteroidal anti-inflammatory drugs, with systemic corticosteroids 41.3% and with disease modified antirheumatic drugs, most frequently methotrexate, 59.9% of the patients. Radionuclide synovectomy was performed in 6.8%, surgery in 6.2% and physical therapy in all the patients. CONCLUSION: Psoriatic arthritis developed in 9.3% of the psoriatic patients. Time interval for establishing the diagnosis was long, and there were no specific laboratory findings. All the synovial joints could be involved in the psoriatic process. Scintigraphy should be used only in case of early suspected sacroiliitis. The treatment of psoriatic arthritis was the teamwork between the dermatologist, rheumatologist, physiatrist and orthopedic surgeon.     

NG-nitro-L-arginine methyl ester-induced potentiaton of the effect of aminophylline on rat diaphragm: the role of extracellular calcium

The role of extracellular calcium in the interaction between intracellular cAMP and nitric oxide (NO)/cGMP on the contractility of rat diaphragm pretreated with cumulative concentrations of aminophylline (0.36 - 3.60 mM) was investigated. In a Ca2+-free medium, NG-nitro-L-arginine methyl ester (L-NAME) (1 and 3 mM) depressed tension developed (Td) and also aminophylline-induced potentiation of Td in a concentration-dependent manner. Verapamil (2.5 microM) or nicardipine (20 microM) significantly antagonized the potentiating effect of L-NAME on Td in a calcium-containing medium. However, in the presence of verapamil or nicardipine, L-NAME still produced statistically significant potentiation of the cumulative concentrations of aminophylline (0.36 - 3.60 mM), given in the second series.     

Antimelanoma immunity in vitiligo and melanoma patients

Cutaneous melanoma and vitiligo are diseases etiology of which evolves around melanocytes. The nature of immunological disturbances associated with these diseases is not elucidated. The experiments performed in this work were aimed to determine antimelanoma immunotoxicity in patients with melanoma and patients with vitiligo. Twelve patients with melanoma, ten patients with vitiligo and seventeen healthy volunteers were studied. The cytotoxicity of PBMC was evaluated indirectly through determination of target melanoma (Fem-x) or control tumor (HeLa) cell survival, in the presence of 15% of AB or autologous sera, by MTT test. The mean values of antimelanoma cytotoxicity in AB serum were similar in both patients groups and in controls. However, the frequency of patients with the enhanced cytotoxicity against melanoma cells, in relation to control tumor cells, was lower in both patients groups than in controls. The intensity of antimelanoma cell-mediated cytotoxicity in melanoma patients, in the presence of autologous serum, was significantly lower in comparison to that found in control subjects and vitiligo patients (p<0.014, in both cases). This indicates that some factors from melanoma patient's sera contribute to impairment of the cytotoxicity of autologous PBMC, while other factors from the serum of vitiligo patients and control subjects enhanced their PBMC antimelanoma cytotoxicity.     

Development of the second-order derivative UV spectrophotometric method for direct determination of paracetamol in urine intended for biopharmaceutical characterisation of drug products

Paracetamol is a widely used nonsalicylate analgesic and antipyretic drug. The existing methods for the determination of paracetamol in biological fluids are mainly HPLC techniques, although there are some reported methods based on spectrophotometric determinations. However, all these methods involve some extraction or derivatisation procedures. In the present study the UV spectra of investigated samples were recorded over the wavelength range 220-400 nm (lambda step 0.21 nm; scan speed 60 nm/min) and second-order derivative spectra were calculated. Second-order derivative spectra of different blank urine samples displayed the presence of a zero-crossing point at 245-247 nm defined as lambdazc. The zero-order absorption spectra of paracetamol in water displays maximum absorbance at 243 nm, while in second derivative spectra, a minimum peak at 246 nm was observed. Therefore, the application of zero-crossing technique to the second-derivative UV absorption spectrum should be useful for the determination of paracetamol using 2Dlambdazc. The proposed method enables determination of total paracetamol in urine directly and simply by reading the 2Dlambdazc of the diluted samples. The obtained results were in good accordance with published data on cumulative urinary excretion after per oral administration of paracetamol obtained applying different spectrophotometric methods of determination. It could be useful for biopharmaceutical characterisation of drug products (monitoring of the levels of paracetamol in urine in bioavailability testing, for the evaluation of in vitro-in vivo correlation and screening of different formulations during drug product development).     

The burden of type 2 diabetes in Serbia and the cost-effectiveness of its management

The purpose of this study was to analyse whether the nationwide application of the national Serbian guideline for diabetes mellitus (NSGDM) would save a relevant amount of disability-adjusted life years (DALYs) and/or reduce the medical cost of treating diabetic patients in Serbia, as compared to the present situation. Disability-adjusted life years were calculated for Serbia and the cost-effectiveness was analysed in eight population groups under ideal and present conditions; prevalent and incident cases were each split up for patients with blood glucose that was well controlled and that was uncontrolled. Under ideal conditions, i.e., according to the NSGDM, 8,031 DALYs could be saved with a potential cost reduction at the same time of approximately 19 million Euros. The implementation of the NSGDM in clinical practice bears a great potential to save lives and reduce years lived with lowered quality of life, but in addition it may reduce costs by about a quarter.     

The antitumor immune response in HER-2 positive,metastatic breast cancer patients

The aim of this study was to determine the basis for anti-tumor immune reactivity observed in patients with human epidermal growth factor receptor-2 (HER-2) (3+) breast carcinoma using an in vitro model in which the role of the HER-2-specific monoclonal antibody Herceptin was also investigated. Patients with metastatic breast cancer who had their primary tumor resected were included in this study. Peripheral blood mononuclear cell (PBMC)-dependent cytotoxicity in the presence or absence of Herceptin were assessed using the survival of target breast adenocarcinoma MDA-MB-361 cells as a parameter in a (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test. We observed a significant increase in PBMC-dependent cytotoxicity when autologous serum was introduced in the assay. Furthermore, the addition of Herceptin significantly increases their cytotoxicity. These data suggest that autologous serum constitutively contains factors that might affect PBMC-dependent cytotoxic activity against HER-2 positive cancer cells.     

Effects of cisplatin and other Pt(II) complexes on spontaneous motility of isolated human oviduct

The toxicity of platinum(II) ion could be significantly modified by coordination with some organic compounds. In our study, the cytotoxicity and the influence of platinum(II) complexes, such as cisplatin, cis-[PtCl(2)(NH(3))(2)], [PtCl(2)(SMC)] and [PtCl(2)(DMSO)(2)] (where SMC is S-methyl-l-cysteine and DMSO is dimethyl sulphoxide) on spontaneous motility of isolated human fallopian tubes were investigated. Cisplatin showed potent pro-apoptotic effects on peripheral blood mononuclear cells (PBMC). However, peripheral blood mononuclear cells were substantially less sensitive to [PtCl(2)(SMC)] and [PtCl(2)(DMSO)], and these compounds showed no toxic effect on PBMC in all concentrations examined. Cisplatin showed concentration-dependent inhibition of spontaneous contractions of the isolated ampulla. (EC(50)=1.14+/-0.03 x 10(-6)M/l, r=0.714, p<0.05) while [PtCl(2)(SMC)] and [PtCl(2)(DMSO)(2)] did not affect spontaneous contractions of isolated fallopian tube ampulla.     

Ability of retroviral transduction to modify the angiogenic characteristics of RPE cells

Background: Retinal pigment epithelial (RPE) cells play an important role in the modulation of ocular angiogenesis. Transduction of RPE cells with retroviral vectors bearing modulating genes can result in long-term transgene expression and may alter the angiogenic characteristics of RPE cells. This study was designed to determine whether changes in angiogenic characteristics of RPE cells result from transduction with retroviral vectors bearing modulating genes, using in vitro angiogenic assays, including analysis of endothelial proliferation and wound healing. • Methods: Human RPE cells were transduced with retroviral vectors bearing either a urokinase-type plasminogen activator (u-PA) or a tissue-type plasminogen activator (t-PA) cDNA. Ten weeks after gene transfer, RPE cells transduced with the u-PA (u-PA-RPE cells) or the t-PA cDNA (t-PA-RPE cells), or untransduced (control) RPE cells, were cocultured with human umbilical vein endothelial cells (HUVECs) by contacting and non-contacting coculture methods. The effects of these cells on proliferation and in vitro “wound healing” of HUVECs were evaluated. • Results: Over 18 weeks, u-PA-RPE cells released large amounts of biologically active u-PA (total amount, 50.2 ± 9.7 ng/10⁶ cells/24 h), while t-PA-RPE cells released large amounts of functional t-PA (15.4 ± 3.2 ng/10⁶ cells/24 h). Control RPE cells did not release any detectable t-PA or u-PA. In the proliferation assay, u-PA-RPE cells stimulated HUVEC proliferation in contacting cell cultures, but not in non-contacting cell cultures. In contrast, t-PA-RPE cells, normal RPE cells or exogenous u-PA had no effect on HUVEC proliferation. In the wound healing assay, u-PA-RPE cells in contacting coculture and exogenous u-PA stimulated wound healing of HUVECs, while non-contacting u-PA-RPE cells, t-PA-RPE cells and normal RPE cells had no effect on HUVEC wound healing. RPE cells transduced with u-PA secreted large amounts of u-PA for as long as 18 weeks, and these cells stimulate HUVEC proliferation and in vitro wound healing. As a result, the angiogenic characteristics of RPE cells can undergo long-term changes. • Conclusions: These results suggest that genetically modified RPE cells can be used to modulate ocular angiogenesis and may have potential for gene therapy of ocular diseases. Received: 3 January 1997 Revised version received: 7 May 1997 Accepted: 26 May 1997