Anti-inflammatory efficacy of low-dose cyclosporin A in psoriatic arthritis. A prospective multicentre study

Summary Fifty-five patients with psoriatic arthritis were treated with a low dose of cyclosporin A (CyA) (mean dose 2.7 mg/kg per day) for a period of 6 months to investigate the efficacy of CyA on disease parameters. Significant improvement in the joint complaints and inflammation parameters was observed including a decrease in the number of painful (-46%) and swollen (-45%) joints, tenderness (Ritchie Index: -50%) and degree of swelling (-46%), patient's assessment of pain (-35%), the duration of morning joint stiffness (-37%), as well as a decrease in C-reactive protein (-52%). A 50% reduction of joint complaints required a total of 24 weeks, whereas a 50% reduction of skin involvement was achieved after 5–6 weeks of treatment. Four patients left the study due to adverse events: creatinine level increase in two patients, hypertension in one patient and gastroenteritis in the fourth patient. Joint scintigraphy in 18 patients indicated an improvement or stable condition in 61% of cases after a mean follow-up of approximately 8 months. The results of this prospective study show that low-dose CyA effectively improves not only skin lesions, but also joint complaints in psoriatic arthritis.     

ACCURACY OF PREDICTING LONG-TERM PROSTATE SPECIFIC ANTIGEN OUTCOME BASED ON EARLY PROSTATE SPECIFIC ANTIGEN RECURRENCE RESULTS AFTER RADICAL PROSTATECTOMY

PURPOSE: We determined how prostate specific antigen (PSA) doubling time changed with time and whether an early measure of doubling time would accurately predict long-term PSA values and clinical outcome in a cohort of patients followed expectantly after radical prostatectomy. MATERIALS AND METHODS: We analyzed data on 121 patients with PSA recurrence after radical retropubic prostatectomy. Group and individual analyses were performed on 60 patients who met study inclusion criteria. PSA doubling time was calculated and a curve was plotted using logarithmic transformation with linear regression and least squares analysis. In analysis 1 patients were placed into 3 subgroups according to doubling time. Doubling time was calculated per subgroup and the slopes of the aggregate curves were compared to determine how doubling time changed with time. In analysis 2 we calculated early doubling time per patient using only the initial 2 detectable PSA values and compared it with eventual doubling time in each using all PSA values. In addition, we analyzed how doubling time correlated with the clinical course. RESULTS: Using the group methodology there was no statistically significant acceleration or deceleration with time in doubling time slope in any of the 3 subgroups. On individual analysis we noted a weak correlation of early with eventual doubling time (correlation coefficient 0.69, p = 0.01). In 88% of patients eventual doubling time was not within 10% of early doubling time. Metastasis developed in 60% of patients with an eventual DT of 0 to 6 months, while 80% with an eventual doubling time of 6 to 12 months had no evidence of local or metastatic disease. No patients with an eventual doubling time of greater than 12 months have had metastatic disease and only 4 (16%) had local recurrence, which was treated with radiation therapy. In 8 of the 14 patients (23%) with local recurrence or metastatic disease early doubling time predicted eventual doubling time. Early doubling time was more rapid and slower than eventual doubling time in 5 and 1, respectively, of the remaining cases, which would have placed them in a different subgroup. CONCLUSIONS: On group analysis PSA doubling time appeared to be constant with time and there was no evidence that it accelerated with time in our dataset of PSA recurrence after radical prostatectomy. On individual analysis early doubling time showed a weak but statistically significant correlation with eventual doubling time. However, there was significant inaccuracy when predicting PSA doubling time based on early PSA values in individuals. Generally early projections of doubling time tend to over predict tumor biological aggressiveness, that is local recurrence or metastasis. A need remains for more accurate predictors of the rate of disease progression at initial PSA recurrence to determine accurately early in the clinical course the patients who may benefit from additional therapy. Currently no patient in our study has died of prostate cancer.     

半夏泻心汤治验

半夏泻心汤在《伤寒论》、《金匮要略》中均有记载,由半夏、干姜、黄连、黄芩、人参、甘草、大枣组成,该方寒温平调,辛开苦降,具有消痞除满之功。是和解少阴之代表方剂之一,半夏泻心汤,临床应用甚广。     

Patient Acceptance of the Implantable Cardioverter Defibrillator in Ventricular Tachyarrhythmias

Besides surgical problems, recipierifs of implantable cardioverter defibrillators (ICDs) are faced with psychological and social adjustments. Successful ICD therapy is influenced by the patients' perceived concerns regarding device, discharge, changes in life style, and complications. In order to assess patients' acceptance of the ICD, the psychological profile of 57 consecutive patients was evaluated using a specifically designed questionnaire and the State Trait Anxiety Inventory (STAI). The results showed that 20 patients staled fear of ICD discharge, 12 patients revealed physical discomfort due to the device, and limited quality-of-life occurred in 8 patients. Fifty-five of 57 patients answered that it was worth having an ICD device implanted, 30 (53%) patients returned to active life, and 56 (98%) would advise another patient to undergo implantation if necessary. Overall, there was only a slight, but insignificant, decrease in the level of anxiety within the total patient population after ICD implantation. However, a comparison of two subgroups indicated that the state of anxiety was significantly higher in patients < 50 years of age as well as in patients having received > 5 shocks versus those > 50 years of age and having experienced < 5 shocks. In general, the acceptance of the ICD as a tool in managing life-threatening ventricular tachyarrhythmias is high. Besides the increased survival rate, quality-of-life and patient acceptance are important criteria for successful ICD therapy.     

A comparative study of the cytotoxicity of skin irritants on cultured human oral and skin keratinocytes

Summary The cytotoxicity of irritants on human oral and skin keratinocyte culture models was compared. Keratinocytes were exposed to sodium lauryl sulphate and benzalkonium chloride at concentrations of 10^–4–10^–7 M for 24 h. Cytotoxicity was evaluated by changes in niitochondrial metabolic activity (MIT assay) and plasma membrane integrity (LDH leakage). Our results showed that oral and skin keratinocytes are equally sensitive to the irritants tested. There were marked similarities in susceptibility between each cell type cultured from six individuals. The immunohistochemical staining pattern of both cell types resembled that of the basal cell.
These observations suggest that the skin keratinocyte culture model may be useful in evaluating the cytotoxicity of agents which are irritants on either the skin or oral mucosa.     

Sulfonation of arginine residues as side reaction in Fmoc-peptide synthesis

Several arginine-rich peptides containing the C-terminus of neuropeptide Y (NPY) were prepared by solid phase peptide synthesis using Fmoc chemistry and cleaved from the resin with trifluoroacetic acid (TFA). The products were characterized by fast atom bombardment-MS, LC-thermospray-MS, ion spray-MS/MS, and Edman degradation. The side products could be identified as peptides with sulfonated arginine residues resulting from an unexpected cleavage of Mtr or Pmc protecting groups. The degree of sulfonation depended on the choice and composition of the cleavage solution. Several scavenger mixtures were used and a mixture of thioanisole/thiocresol was found to be the most efficient for suppressing sulfonation. Furthermore treatment with the enzyme arylsulfate-sulfohydrolase desulfonated the peptides yielding the correct sequence.     

Skeletal muscle and whole body protein turnover in thyroid disease

The effects of disturbances of thyroid hormone secretion on leg and whole body amino acid and protein metabolism have been investigated in seven patients with untreated thyrotoxicosis and eight patients with untreated hypothyroidism; the results were compared to those obtained in 11 normal control subjects. After treatment, the patients were restudied. Arterio-venous exchanges of tyrosine and 3-methylhistidine across leg tissue in the post-absorptive state were used as indices of net protein balance and myofibrillar protein breakdown, respectively. Whole body protein turnover was measured using stable isotope labelling techniques with 1-[1-13C] leucine. Efflux of tyrosine from leg tissues was six-fold greater in patients with untreated thyrotoxicosis than in normal control subjects (-19.39 +/- 2.21 vs. -4.20 +/- 0.31 nmol 100 g-1 leg tissue min-1, P less than 0.005, mean +/- SEM), but 3-methyl-histidine efflux was not significantly different (-0.11 +/- 0.03 nmol 100 g-1 leg tissue min-1 vs. 0.14 +/- 0.02 nmol 100 g-1 leg tissue min-1). After treatment, when the thyrotoxic patients became euthyroid, tyrosine efflux was normalized (at -4.94 +/- 0.84 nmol 100 g-1 leg tissue min-1) and 3-methylhistidine efflux was unchanged. In hypothyroid patients, neither tyrosine nor 3-methylhistidine effluxes were significantly different from those in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of rosmarinic acid on atopic dermatitis

Rosmarinic acid is known to have anti‐inflammatory and immunomodulatory activities. This study was performed to evaluate the effect of rosmarinic acid on atopic dermatitis (AD), one of the inflammatory disorders of the skin. Twenty‐one subjects (14 women and seven men, 5–28 years of age) with mild AD participated in this study. Rosmarinic acid (0.3%) emulsion was topically applied to the elbow flexures of AD patients twice a day (once in the morning and once in the evening). All subjects were evaluated for skin conditions before treatment at the first visit, and then at 4 and 8 weeks after treatment. According to local Severity Scoring of Atopic Dermatitis index results, erythema on antecubital fossa was significantly reduced at 4 and 8 weeks (P < 0.05). Transepidermal water loss of the antecubital fossa was significantly reduced at 8 weeks compared to before treatment (P < 0.05). The results from self‐questionnaires on the efficacy of rosmarinic acid indicated that dryness, pruritus and general AD symptoms improved. Our investigation into the AD‐mitigating effect of rosmarinic acid through in vivo experiments demonstrated the possible clinical use of rosmarinic acid as a therapeutic agent for AD.