Soluble CD30: a biomarker for evaluating the clinical risk versus benefit of IFNbeta1A treatment in multiple sclerosis patients.

Aberrant redox regulation occurs in immune and neurological pathologies, hence targeting the pathways involved in the regulation of the redox system could provide further insights into these diseases and open up new avenues for therapy. Soluble (s) CD30 is of key clinical importance in this respect, as its levels reflect the functionality of the CD30 receptor (CD30R), the specific lymphocyte receptor for thiol disulfide/oxidoreductase thioredoxin 1 (Trx1) which is known to regulate important immune and neurological processes. Increased levels of sCD30 appear to be a common element of oxidative stress, immunological alterations and neurological deficit, therefore these increases could be used as a clinical biomarker and target for therapy. We targeted sCD30 in our study of dendritic cell (DC) regulation of the T helper (Th) cell network in multiple sclerosis (MS) patients, as abnormalities in T regulatory (Treg)/Th1/Th17 pathways contribute to the pathogenesis of this immunological/neurological disease. DC profiles in Treg/Th1/Th2/Th17-types of cytokine production in culture supernatants were used as they determine the type of Th differentiation. Our results show that sCD30 levels increase significantly in MS patients, reflecting the disruption in the regulation of the Treg/Th1/Th17 cell network. A fall in the level of soluble CD30, induced by IFNbeta1a therapy, opposed the increase of neurological deficit through increasing IL10 and TGFbeta levels, thus re-establishing network homeostasis but only when this was accompanied by an increase in IL12p70 levels. Since IL12p70 cytokine production is regulated by Trx1, our results indicate that redox system alterations may be the cause of IFNbeta1a therapeutic inefficacy. We conclude that an increase in the level of IL10, TGFbeta and IL12p70 and a fall in the level of sCD30 represent a means of evaluating the clinical risk/benefit of IFNbeta1a treatment.

Complete response in advanced breast cancer patient treated with a combination of capecitabine, oral vinorelbine and dasatinib.

BACKGROUND: Currently, there are no data available on the best choice of treatment in heavily pretreated patients with advanced breast cancer. However, the combination of oral vinorelbine and capecitabine has been demonstrated to be effective and safe in patients with advanced breast cancer pretreated with anthracycline. Furthermore, some studies assessed the activity of dasatinib, an oral tyrosine kinase inhibitor that inhibits five oncogenic tyrosine kinase families, alone or in combination with different chemotherapy in patients affected with advanced breast cancer. CASE PRESENTATION: A patient with metastatic breast cancer, hormone receptor positive and human epidermal grow factor receptor 2 negative, pretreated with epirubicine, taxanes and nab-paclitaxel, was submitted to third line chemotherapy with vinorelbine 60 mg/m2 on day 1, 8 plus capecitabine 1000 mg/m2 twice daily from day 1 to day 14 every 21 days. The patient was taking also dasatinib 100 mg once daily for chronic myeloid leukemia. The treatment was well tolerated and, after 15 months, computed tomography scan showed a complete response of liver metastases and bone stable disease. After another 28 months, a 18-fluorodeoxyglucose positron emission tomography scan showed a metabolic response of bone metastases without other site of disease. CONCLUSIONS: This is the first case in literature about activity of dasatinib in combination with a chemotherapy schedule of oral vinorelbine and capecitabine in advanced breast cancer. This treatment showed both good tolerability and great activity with a long progression free survival of 54 months.

[Laparoscopic promontal fixation: assessment of 100 cases]. / Promontofissazione laparoscopica: valutazione di 100 casi.

AIM: Aim of the study is to evaluate long term results of 100 patients treated laparoscopically to repair genital prolapse and urinary incontinence. METHODS: A retrospective review analysis of 100 women, who underwent laparoscopic genital prolapse repair at Primary Referral University Hospital in Clermont-Ferrand. Patients characteristics, preoperatory exams, intraoperative, postoperative and outpatient clinic data were collected and analyzed. RESULTS: The mean operative time was 172 minutes. One laparotomy conversion was required, due to a technical problem. The mean hospitalization stay was 4.7 days. Two patients required a reintervention during their hospitalization stay, due to a complication. All the patients were reviewed during the 6 months later the intervention. The follow-up is between 6 months and 3 years. The average degree of cystocele and hysterocele was ameliorated from stage 3 to stage 0, the average stage of rectocele was ameliorated from stage 2 to stage 0, finally the average stage of vault prolapse was ameliorated from stage 1 to stage 0. The incidence of genuine stress incontinence was 47% in the preoperative time and only 4% at the long follow-up. We had a total 4% rate of mesh vaginal erosion. CONCLUSIONS: The laparoscopic sacrocolpopexy is an effective and safe technique to repair the major pelvic prolapses.

Clinical experiences in the treatment of pain in rheumatology.

Meclofenamic acid is an analgesic endowed with anti-inflammatory properties. Its main activity is the combined inhibition of leukotrienes and prostaglandins synthesis, yet it is also able to antagonize the peripheral effects of prostaglandins. This particular feature explains why the effect of this drug is so fast, especially when administered orally. The pharmacological properties and good tolerability of meclofenamic acid propose the use of this drug for the treatment of various types of pain, particularly at osteoarticular localization. Recent comparative studies with meclofenamic sodium versus placebo, indomethacin, oxyphenbutazone, and diclofenac confirmed that meclofenamate sodium is very effective, significantly reducing pain as well as the subjective and objective symptoms accompanying it. The findings of these studies have also highlighted a particularly favorable safety profile. Our study primarily focused on assessing the effectiveness and tolerability of this drug in 82 patients affected with extraarticular rheumatism localized in various sites. Meclofenamic acid (as a sodium salt) was orally administered in doses of 100 mg twice daily for 2 weeks. The assessment of the drug's clinical effectiveness took into account the various aspects of pain (spontaneous, on motion, due to active contrasted movements) and quantified it using a 5-point rating scale (0 = absence of pain; 5 = very intense pain). At the end of the 2-week observation period, both the investigator and the patient gave their opinion as to the effectiveness and tolerability of the drug. The treatment was found to be highly effective in reducing pain in 59.7% of the patients, regardless of the nature and location of the rheumatic process. Tolerability was rated good-to-excellent in 72% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell cycle control in cellular homeostasis during the immune response: interactions between TH1, TH2 cytokines, and Bcl2 and p53 molecules.

Cytokine regulation of lymphocyte survival may play an important role in the control of the cell cycle during the immune response both in health and disease. Expression of the Bcl2 gene promotes cell survival by countering apoptosis stimuli. The p53 protein has been implicated in the control of the cell cycle, in the synthesis and repair of DNA and in programmed cell death. TH1 and TH2 cytokines exert a mutual cross-regulation on the precursors of TH1- or TH2-type effector cells which are important mediators in directing the immune system towards the appropriate response. TH1 and TH2 cytokines have also been implicated in the modulation of the expression of cell cycle regulator genes. Therefore, the study of the relationships between TH1 and TH2 cytokines and Bcl2 and p53 molecules in healthy subjects could lead to a better understanding of the physiological regulation of the immune response and identify markers for prognostic and diagnostic indices and biotherapeutic treatment. We determined the serum levels of cytokines (IL2, IFN gamma, IL4, IL10, IL5, IL6, IL1 beta, TNF alpha, IL8), soluble receptors (sIL2R, sIL6R), Bcl2-protein and p53-antibody in a group of healthy subjects. Multivariate statistical analyses were used to study the cytokine network relationships with Bcl2-protein and p53-antibody, as they allow a simultaneous evaluation of all variables which reflects the physiological situation. Our overall results suggest that relationships exist between TH1 and TH2 cytokines and the Bcl2-protein and p53-antibody in physiological conditions. This information could now be used in experimental studies to create diagnostic and prognostic indices for the monitoring of health and disease.

IL-10 and sIL-2R serum levels as possible peripheral blood prognostic markers in the passage from adenoma to colorectal cancer.

The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for the early detection of disease. Adenomas have been identified as precursors of colorectal cancer and tumor establishment, and disease progression has been found to reflect a malfunction of the immune system. We previously indicated the investigation of cytokine serum levels in these patients as a useful and non-invasive tool for the study of the disease progression and an imbalance at TH1 and TH2 cell levels was also found. Moreover, the soluble form of interleukin (IL) 2 receptor (sIL-2R) level is an in vivo marker of T cell activation and is used to monitor the activation of the immune system. We therefore performed an immunological study on a group of healthy subjects, subjects with adenomas, and colorectal cancer patients to identify peripheral blood invasiveness markers in the progression from normal mucosa through adenoma to tumor. In this paper we evaluated the relationships between serum levels of interleukin IL-2, sIL-2R, interferon (IFN) gamma, IL-4, IL-6, IL-10 and sICAM-1 and their networks. Our overall data indicate that in the normal mucosa through adenoma to tumor progression, the host immune response proceeded from a TH1 cell-mediated immune response type (healthy subjects) to a type with TH2 suppressive characteristics (adenoma subjects and cancer patients). However, in the adenoma subjects there was no IL-10 or sIL-2R involvement, while these parameters were implicated in the cancer patients' immune responses. Moreover, a concurrent augmentation of sIL-2R and IL-10 levels seems to be prognostic for the passage from adenoma to cancer, and the sIL-2R and sICAM-1 molecules appear to be involved in the invasiveness mechanisms.

The role of the soluble CD30 serum level in colorectal cancer: a possible marker for a patient subset which could benefit from IL-2 biotherapy.

On the basis of our previous data suggesting an impairment in host immune response in colorectal cancer caused by an inappropriate switch from TH1 towards TH2 cells, we investigated the role of the soluble CD30 (sCD30) in this disease, as this molecule was found related to immune responses characterized by the activation of a prevalence of TH2 cells. We studied a group of healthy subjects and colorectal cancer patients determining the sCD30 serum level and the following immunological parameters: s interleukin-2 receptor (sIL-2R), IL-2, interferon (IFN) gamma, IL-6, IL-4 and IL-10 levels in the serum and peripheral blood mononuclear cell (PBMC) production; PBMC proliferative responses to IL-2, anti-CD3 monoclonal antibody (CD3) and IL-2 + CD3. Our overall data indicate that in colorectal cancer the sCD30 serum level is also linked to a prevalence of the TH2 immune response activation. However, the Multivariate statistical study underlines that the sCD30 level is principally related to the IL-6 TH2 cytokine. Moreover, it suggests that in colorectal cancer, the sCD30 level might be a marker for identifying a patient subset in which IL-2 biotherapy treatment could contribute to the restoration of the impaired immune system.

Prognostic significance of immunological evaluation in colorectal cancer.

According to the concept that tumour establishment and progression generally reflects a malfunction of the immune system, we have investigated the prognostic significance of immunological parameters in correlation to stage progression in colorectal cancer. In patients and healthy subjects as control group, we determined: serum levels of interleukin (IL)-2, interferon (IFN) gamma, IL-4, IL-6, IL-7, IL-8, tumor necrosis factor (TNF) alpha cytokines and soluble IL-2 receptor (sIL-2R), CD30 (sCD30), ICAM-1 (sICAM-1) molecules, phenotype of peripheral blood mononuclear cells (PBMC); PBMC proliferative response to IL-2, IL-4 and anti-CD3 monoclonal antibody (anti-CD3) variously combined. Our results show that, compared to healthy controls, the group of all patients, but interestingly, also the groups of patients at the various stages of the disease, seem to have different values of these immunological parameters. Since tumour invasion and metastasis are the major causes of cancer treatment failure the early recognition of preinvasive states could lead to an improvement in prognosis. For this purpose our results might be especially useful in making prognostic and diagnostic indices in this neoplasy to identify patients at risk for tumour detention and the patient condition concerning disease progression by a non-invasive method. Moreover, this evaluation which contributes to identify the damage in the patient immune response to tumor could be helpful in identifying the therapeutic substances which might switch this response from being unproductive to productive. Thus, our data leads us to indicate that it might be possible to define reliable prognostic and diagnostic indices in colorectal cancer from the extension of this immunological study by the evaluation of these and other parameters.

Immunological directives for biotherapy improvement in the treatment of colorectal cancer.

A major cause of failure in biotherapy in cancer may be the non-existence of predictive indices to individualize the substances which might be helpful to switch the patients' immune response to tumour from an non-productive to a productive one. The defect in the patients' immune system needs to be identified and so the evaluation of their responses to biotherapeutic agents, in correlation to the disease progression is essential. We have addressed this problem in colorectal cancer at systemic level by examining the proliferative response of peripheral blood mononuclear cells (PBMC) to interleukins (IL) IL-2, IL-4, antiCD3 monoclonal antibody (antiCD3), IL-2+CD3, IL-2+IL-4, IL-4+CD3, IL-2+CD3+IL-4; the PBMC expression of phenotypic antigens CD3, CD4, CD8, CD25, DR, CD16, CD56, CD57 and CD19 in the patients and healthy subjects as control group. Analysing our data, it seems that as the disease progresses in these patients the peripheral blood cells change their ability to respond to activation agents which appears to be due to a phenotypic modification of their subsets. Our overall results might give a possible explanation of the variable responses to biotherapy in colorectal cancer patients.

The TH1 and TH2 cytokine network in healthy subjects: suggestions for experimental studies to create prognostic and diagnostic indices for biotherapeutic treatments.

In vivo and in vitro studies have demonstrated the selective regulatory effect that TH1 and TH2 cytokines reciprocally exert in the regulation of the polarization of precursor cells into TH1 or TH2 types. The study of the network relationships between TH1 and TH2 (TH1/TH2) cytokines in healthy subjects could lead to a better understanding of how the physiological network of cytokines regulates the immune response. Such study could lead to gain suggestions for follow-up experiments to create prognostic and diagnostic indices for biotherapeutic treatments of patients. Hence we determined serum levels (environment network) and PBMC production (cellular network) of IL2, IFN gamma, IL4, IL6 and IL10 in the peripheral blood of healthy subjects; these cytokines made up our networks under basic conditions. Both men and women were studied as hormones can influence the polarization of TH1 and TH2 cells. Cytokines within the physiological network function simultaneously so multivariate statistical methods were used to study TH1/TH2 relationships. The use of mathematical modelling is the only effective way of studying the immune system as a whole. The physiological TH1/TH2 network under activation conditions was evaluated by incorporating: sIL2R and sIL6R into the basic environment network model and the production levels of cytokines by PBMC after PHA stimulus, into the basic cellular network model. The influence of APC was evaluated by adding: serum levels of TNF alpha and IL1 beta to the environment network model, and production levels of IFN gamma, IL10 and IL6, after stimulus with LPS, to the cellular network model. Our results led us to hypothesize that the physiological network of TH1/TH2 cytokines regulates TH polarization by means of specific relationships between TH1 and TH2 cytokines, which may be different in men and women. These relationships could be studied experimentally to create prognostic and diagnostic indices for more efficient prevention programs and biotherapeutic treatments of patients.

Disease stage prognostic indices in the early clinical screening of colorectal cancer patients.

It is a truism to state that in cancer the extent to which the disease has spread (stage) is probably the most important factor determining patient prognosis and must be given prime consideration in evaluating and comparing different therapeutic regimes. Because of this, clinical screening tests (such as a rectal exam proctoscopy and colonoscopy), if tissue that is not normal is found, should include analyses contributing to the patient disease stage classification. However, the difficulty involved in this, principally due to the absence of reliable early prognostic indices of the disease stage, makes the cancer patients' treatment full of problems and risks. By a retrospective statistical study on pre-surgery peripheral blood immunological parameters of our groups of colorectal cancer patients and healthy subjects, we evaluated our previously suggested possibility of defining stage prognostic indices by parameter blood range values, evaluating their ability in the stage classification compared to the pTNM method. We have investigated the serum levels of various cytokines and cytokine receptors, leukocyte surface markers, peripheral blood mononuclear cell (PBMC) cytokine production and PBMC proliferative response. Statistically significant correlations between a variety of these immunological parameters and the disease stage were found, but as a clinical patient screening of all parameters is quite expensive, to identify the greatest stage weighting parameter and the respective blood range values, we performed a multivariate statistical analysis. We found that the blood ranges of IL-4 serum level and the PBMC proliferative response to anti-CD3 monoclonal antibody (mCD3) stimulus may be reliable prognostic indices which may contribute to an early disease stage classification in colorectal cancer patients, since they seem to be valid as the pTNM method. Moreover, as the immunological prognostic indices could be a useful tool to evaluate the patient immune response, they may also improve the definition of the patient's stage classification for the selection of treatment and restaging procedures for the evaluation of the treatment benefit and recurrent disease.

Bcl-2 and drugs used in the treatment of cancer: new strategies of biotherapy which should not be underestimated.

The theory that an imbalance in the control of the cell cycle contributes to the appearance and progression of neoplastic disease is gaining more ground all the time. This new line of research into tumor disease is a result of the progress made in the comprehension of cell death (apoptosis) and the discovery of alterations in the apoptotic pathway in patients with cancer, which have also been correlated to disease mechanisms. Alterations in the cycle of events that brings about apoptosis can result in tumor cells resistant to chemotherapy. In fact one of the inherent risks of chemotherapy is the generation of new, more aggressive, clonal variants and destruction of healthy cells with deleterious effects on the organism. This review examines the results of studies concerning the identification of the alterations in apoptotic mechanisms in carcinogenesis and the mechanisms governing their regulation. The aim was to evaluate if such data could be of use in identifying drugs able to improve cancer treatment.

Relationships between the activity of MMP1/TIMP1 enzymes and the TH1/TH2 cytokine network.

The evaluation of the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) would appear to be important in cancer patients. Since the activity of these enzymes is regulated at the gene level by cytokines, we studied the serum relationships between MMP1/TIMP1 and the network of TH1/TH2 cytokines in healthy subjects to better understand how the physiological network of cytokines regulates MMP1/TIMP1 activity. Such a study could lead to suggestions for follow-up experiments to create prognostic and diagnostic indices for more efficient disease prevention programs and biotherapeutic treatments of patients. For this purpose, we determined serum levels of MMP1, TIMP1 and interleukin (IL)2, interferon (IFN) gamma, IL4 and IL10 in both healthy men and women (men and women were analyzed separately as hormones are one of the non-cytokine regulatory factors of TH1 or TH2 polarization). These cytokines make up our basic network. Cytokines within the physiological network function simultaneously so mathematical models of multivariate statistical methods were used to study MMP1/TIMP1 and TH1/TH2 network relationships. It has been suggested that mathematical modeling is the only effective way of studying the immune system as a whole. The influence of network activation, antigen presenting cells, antibody response and chemokines on MMP1/TIMP1 balance was also studied. Network activation was evaluated by measuring the levels of soluble IL2 receptors (sIL2R) and sIL6R; the influence of antigen presenting cells was evaluated by measuring serum levels of tumor necrosis factor alpha (TNF alpha) and IL1 beta; antibody response was evaluated by measuring IL5 and IL6 serum levels and the influence of chemokines was evaluated by measuring serum levels of IL8. Our overall results suggest that there are relationships between the activity of MMP1/TIMP1 and the TH1/TH2 network in physiological conditions. These data may be useful in gaining a clearer insight into how the two systems interact and hence regulate the physiological homeostasis. Therefore, this paper provides suggestions for experimental studies on MMP1/TIMp1 enzymes and TH1/TH2 cytokines to create clinical and prognostic markers for patient evaluation.

The sCEA molecule suppressive role in NK and TH1 cell functions in colorectal cancer.

The soluble form of carcinoembryonic antigen (sCEA), an oncofetal glycoprotein, is frequently produced by human epithelial-tumor cells, particularly of colorectal origin, and evaluated as a prognostic index of tumor progression and patient survival. sCEA molecules are often present at high concentrations in the peripheral blood of colorectal cancer patients, but the function and significance of this are not well understood. Reported data have demonstrated that sCEA can interfere in NK-cell/tumor-cell interaction by drastically reducing the lysis of tumor cells in a dose-dependent manner and can also suppress T and B cell functions. The aim of our study was to evaluate this situation in colorectal cancer by determining peripheral blood immunological parameters in a group of patients and healthy subjects. We evaluated the interleukin (IL)-2, interferon (IFN) gamma, IL-4, sIL-2R and IL-10 levels in the serum and the release of IFN gamma, IL-4 and IL-10 from peripheral blood mononuclear cells (PBMC); the PBMC expression of CD3, CD16 and CD19 phenotypic antigens; the PBMC proliferative responses to IL-2, IL-2 + anti-CD3 monoclonal antibody (mCD3) and mCD3. The statistical evaluation of our overall results strongly indicates that the high level of the sCEA molecules in the patient's serum might act as a suppressive factor for NK and TH1 immunocompetent cells. This may be the cause of sCEA involvement in tumor progression, and indicates the possibility of an improvement in cancer treatment through its manipulation.

Necessity of biotherapeutic treatments inducing TH1 cell functions in colorectal cancer.

Our previous data on colorectal cancer suggest that there are faults at the level of mechanisms of the proliferative responses of patients peripheral blood mononuclear cells (PBMC) to the interleukin (IL)-2 and IL-2 PBMC production, which increase with the stage advancement. The damages in the proliferative response seem to be eliminated by the costimulator effects of the signals produced by the anti-CD3 monoclonal antibody (antiCD3), and the disregulation in TH subsets of CD4+ T cells with a malfunction of TH1 cells and an expansion of TH2, might contribute to this situation. So, by using biotherapeutic treatments to allow the generation of productive immune response in these patients it is essential to identify the defect in their immune system to discover how these mechanisms should be appropriately manipulated in vivo to switch their immune response from a non-productive to a productive one. We have studied this in a group of patients and healthy subjects as the control group, performing their immunological evaluation by determining these parameters: serum levels of IL-2, interferon (IFN) gamma, IL-4, IL-6, IL-7, IL-8, tumour necrosis factor (TNF) alpha, soluble IL-2 receptor (sIL-2R), intercellular adhesion molecule 1 (sICAM-1) and CD30 (sCD30) molecules; PBMC phenotypic antigens expression (CD3, CD4, CD8, CD19, CD16, CD56, CD57, CD25) on peripheral blood mononuclear cells (PBMC); proliferative response of PBMC to IL-2, IL-4 and anti-CD3 monoclonal antibody (antiCD3). Moreover, since mutant c-Ki-ras oncogene is a very frequent finding in colorectal cancers and there are indications which suggest its involvement in tumour progression, the analysis of c-ki-ras codon 12 and 13 were determined and the statistical evaluation of the above immunological parameters were performed by comparing the patient groups with (M+) and without (M-) these mutations with each other, and with the healthy group. The results underline the necessity of biotherapeutic treatments inducing TH1 cell functions in these patients. Moreover in M+ it seems also important to solve the problem of the switch from B to macrophage cells as immune cells which present antigens, and the possible involvement of c-Ki-ras gene mutations in the impairment of T cell receptor activation (TCR).

Computed tomography of free pleural effusions.

Forty-three CT examinations of the thorax of patients referred for pleural effusion were reviewed. Both normal and thin irregularly thickened pleurae were associated with either neoplastic or non neoplastic disease. In these cases surgery, fine needle biopsy or pleuroscopy may be recommended, their performance being facilitated by the knowledge of the CT findings. Focal pleural masses or thick irregular pleura were consistently associated with malignancies; however, it was not possible to differentiate between primary and secondary forms. The simultaneous imaging of pleura, lungs and mediastinum by CT is very useful for the diagnosis, prognosis, staging and therapeutic approach of neoplasms.

Metastatic renal cell cancer treated with recombinant alpha 2a interferon and vinblastine.

42 patients with advanced renal cell carcinoma were treated with a combination therapy with interferon alpha 2a (mean dosage 16 x 10(6) U i.m. 3 times/week) and vinblastine (0.1 mg/Kg every 21 days). 12 patients (28.5%) had a positive response. Of them 1 presented a complete response (2.38%), 5 a partial response (11.9%) and 6 a stable disease (14.2%). No significant side effects were observed apart from the flu-like syndrome (all patients) and a moderate leukopenia (45.2%). The median duration of responses was 10+ months (range 3-37 months). At 4-year follow-up the median survival time was 16.0 months (range 4-37 months).

Indoprofen in rheumatic patients with acute episodes: a multicentre trial.

The results are reported of an open multicentre trial in 228 rheumatic patients with flare-ups. Fourteen centres adopting the same investigational protocol collaborated in the study. Indoprofen was administered for 1 week at a daily dosage of 1000 mg according to a treatment schedule used with success in acute gouty arthritis: a 400 mg i.v. bolus was followed by 200 mg (1 tablet) t.i.d. Subjective (pain) and objective variables were used for reliable assessment of activity. Marked reduction of pain intensity was already noticeable on day 1 of treatment and was followed by progressive improvement in subjective and objective variables for all the diagnoses considered. According to the patients' own overall assessments, results were good or very good in more than 50% of cases. The best outcomes were obtained in low back pain, acute gout and psoriatic arthritis. At the end of treatment only 7.4% of patients experienced no change or deterioration of symptoms. Adverse reactions, consisting mostly of mild and reversible gastrointestinal disturbances, were reported by 9.2% of patients, but only in 1.8% was treatment discontinued. Indoprofen administered according to the above schedule is an appropriate treatment for acute episodes of rheumatic diseases.

Use of dynamically coated capillaries for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine using capillary electrophoresis.

A rapid, accurate, precise, reproducible, economical, and environmentally gentle method using capillary electrophoresis (CE) is presented for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine in seized drugs. The methodology uses a 32 cm by 50 microm capillary (length to detector 23.5 cm) with a commercially available buffer kit and diode array UV detection. Dynamic coating of the capillary surface is accomplished by flushing with base for 1 min, a proprietary polycation for 1 min, and then a proprietary polyanion for 2 min. This approach provides a relatively high and stable electroosmotic flow (EOF), even at low pHs. The background electrolyte (BGE) contains 75 mM phosphate buffer (pH 2.5) with the same polyanion as above. Using this methodology, amphetamine, methamphetamine, MDA, MDMA, MDEA, and an internal standard (n-butylamphetamine) are baseline resolved in less than 5 min. The run-to-run migration time %RSDs and peak area %RSDs are typically <0.3% and <2.1%, respectively. The day-to-day and capillary-to-capillary migration time %RSDs are <1.5% and <2.1%, respectively. The %RSDs of the relative migration times compared with the internal standard on a day-to-day and capillary-to-capillary basis are <0.2% and <0.06%, respectively. The linear dynamic range using peak areas range from 0.003 to 0.10 mg/mL. The correlation coefficients are >0.9998, with all calibration curves passing at or near the origin. Similar data are obtained for cocaine and its internal standard henyltoloxamine. None of the compounds usually encountered in illicit samples interfere with the target compound (e.g., methamphetamine and cocaine) or the internal standard. Quantitative results for synthetic mixtures and seized exhibits are in good agreement with actual values, and also with results obtained from other techniques. The relatively high EOF for the dynamically coated capillary system allows for the screening of basic, acidic, and neutral adulterants in drug seizures; identification is facilitated by the use of automated UV library searches.

[Clinical study of patients with primary polyarthritis. Cross-over comparative study of proglumetacin and naproxen]. / Studio clinico in pazienti affette da poliartrosi primaria. Confronto in cross-over tra proglumetacina e naproxen.

Proglumetacin at low-dose (300 mg/day) and naproxen (500 mg/day) were used in a crossover study in 20 patients with primary polyarthrosis. Each drug was administered during 1 week without between drugs. Both drugs resulted effective in the management of the most disturbing symptoms, without significant differences. Tolerance was also superimposable, as the few reported complaints were recorded under both treatments and appeared rather related to the patient than to the drug. Proglumetacin therefore, even when given at low dose, resulted at least as effective as an established treatment for polyarthrosis, while confirming its very good tolerance, so as to appear well suited for the general management of patients with such degenerative-reactive disorders.