Chronic urticaria with high IgE levels: first results on oral cyclosporine A treatment.

INTRODUCTION: Chronic Urticaria is a difficult to define condition from the nosographic standpoint, with complex pharmacological management, that heavily impacts the life of the patient. Some forms show not to be responsive to anti H1 anti-histaminic and require other treatments. One of these can be the treatment with Cyclosporine A (CsA). MATERIALS AND METHODS: This study, open and sequential, reports the results of short-term treatment over a sample of adults (21 patients) of both sexes, all suffering from chronic urticaria with IgE levels higher than 200 mU/ml treated with 4 mg/kg/die of CsA. RESULTS: The results obtained show a reduction in the levels of total IgE and a significant improvement in symptoms; there were no adverse effects. CONCLUSIONS: Cyclosporine is an excellent treatment for chronic urticaria because it reduces the activity of T lymphocytes and reduction of the histamine release from the mast cells and basophils.

Acupuncture in clinical and experimental reproductive medicine: a review.

BACKGROUND: Acupuncture has been used as treatment for infertility for hundreds of years, and recently it has been studied in male and female infertility and in assisted reproductive technologies, although its role in reproductive medicine is still debated. AIM: To review studies on acupuncture in reproductive medicine, in experimental and clinical settings. METHODS: Papers were retrieved on PubMed and Google Scholar and were included in the review if at least the abstract was in English. RESULTS: There is evidence of benefit mainly when acupuncture is performed on the day of embryo transfer (ET) in the live birth rate. Benefit is also evident when acupuncture is performed for female infertility due to polycystic ovary syndrome (PCOS). There is some evidence of sperm quality improvement when acupuncture is performed on males affected by idiopathic infertility. Experimental studies suggest that acupuncture effects are mediated by changes in activity of the autonomic nervous system and stimulation of neuropeptides/neurotransmitters which may be involved in the pathogenesis of infertility. CONCLUSIONS: Acupuncture seems to have beneficial effects on live birth rate when performed on the day of ET, and to be useful also in PCOS as well as in male idiopathic infertility, with very low incidence of side effects. However, further studies are necessary to confirm the clinical results and to expand our knowledge of the mechanisms involved.

[The estimation of cardiovascular risk in hypertensive patients is not modified by management of the hypertension]. / L'estimation du risque cardiovasculaire chez des patients hypertendus ne modifie pas la prise en charge de l'HTA.

OBJECTIVES: To compare antihypertensive therapeutic strategies and efficacy whether the physicians were aware or not of the calculated cardiovascular risk at 10 years obtained from the Framingham equation. It was also possible to evaluate the concordance of the general physicians estimation of the cardiovascular risk with the calculated percentage. METHODS: The participation of 953 general physicians to the study allowed to achieve an estimation of the absolute cardiovascular risk for 1,243 hypertensives. Patients were randomised in 2 groups according to the knowledge or not by the physicians of the calculated risk. The therapeutic strategy included a monotherapy (Fosinopril 20 mg/days) for a follow up of 8 weeks, with the possibility to increase the treatment after 4 weeks (Fosinopril + hydrochlorotiazide). To be included, patients had to be more than 18 and less than 75 years, and a blood pressure above 140/90 mmHg. Estimated and calculated cardiovascular risk at 10 years, were classified according to the 1999 WHO-ISH guidelines: low risk < 15%, medium risk 15-20%, high risk 20-30%, very high risk > 30%. RESULTS: In this population, aged 60 +/- 10 years, with 54% of men, the concordance between estimated risk and calculated risk was of 35%. This concordance was better for the "low risk" and "very high risk", but remains inferior to 50%. The determinants of concordance were: gender (male), smoking and a low HDL cholesterol. After 8 weeks of treatment, no difference was observed between the 2 groups concerning final blood pressure level, percentage of normalised patients and number of patients with bi-therapy. CONCLUSIONS: General physicians estimation of cardiovascular risk at 10 years of hypertensive subjects has a bad concordance with the calculated risk according to Framingham equation. The results of this study indicate that the estimation of cardiovascular risk of hypertensive subjects does not modify the management of hypertension.

[Are the 1999 World Health Organization-International Society of Hypertension recommendations applicable to clinical practice?]. / Les recommandations de l'OMS-ISH 1999 sont-elles appliquées en pratique clinique?

UNLABELLED: The aim of the 1999 WHO-ISH guidelines is to help the physicians in the management of hypertensive patients. The institution of antihypertensive treatment represents an important stage of this management sometimes at the detriment of lifestyle measures (non pharmacological treatments). OBJECTIVES: To evaluate if the 1999 WHO-ISH guidelines concerning the initiation of antihypertensive treatment are applied in a hypertension clinic. METHODS: Seventy hypertensive subjects never treated by antihypertensive drugs, aged 51 +/- 13 years, managed in daily hospitalization, were included in the study. According to their level of cardiovascular risk, we evaluated the concordance between the 1999 WHO-ISH guidelines and the clinical practice in term of institution of treatment. RESULTS: A concordance of 70% between the 1999 WHO-ISH guidelines and the clinical practice was observed (50/70 subjects) and a discordance in 30% of cases (20/70). Among the discordant subjects, the treatment was instituted in 65% of cases although it was not recommended. In contrast, in the remaining 35% of cases, lifestyle measures have been proposed although an antihypertensive treatment was recommended. The principal determinants of the discordance were the grade 2 of hypertension, the presence of 1 or 2 risk factors and an enhanced cardiovascular risk (> or = 3 risk factors). Neither age, nor gender were an explicative parameter of the observed discordance. CONCLUSIONS: The 1999 WHO-ISH guidelines concerning the initiation of antihypertensive treatment are more often applied in clinical practice. However, in some cases of grade 2 hypertension drug treatment is more often prescribed than recommended by guidelines, and not enough in the presence of numerous cardiovascular risk factors.

[Hyperammonemia during hypothyroidism: an unusual biohumoral finding normalized by hormonal replacement treatment]. / Iperammoniemia in corso di ipotiroidismo: un insolito reperto bioumorale normalizzato con il trattamento ormonale sostitutivo.

In this paper we describe 3 clinical cases of hypothyroidism causing myopathy and hyperammonemia. The patients, all females, aged 32 to 64 years, presented with hoarseness, fatigue, dyspepsia (case I), difficulty speaking secondary to the sensation of tongue swelling and hoarseness (case II), and progressive weight gain and difficulty speaking secondary to tongue swelling after delivery (case III). Laboratory tests showed a marked increase in creatine phosphokinase (up to 4090 U/L; normal values 24-176 U/L) of muscle origin, and an increase in transaminases and ammonia (124 to 150 micrograms/dL; normal values up to 75 micrograms/dL). Hypothyroidism was confirmed by TSH > 100 microIU/mL (normal values 0.3-5 microIU/mL). Treatment only with L-thyroxine determined the complete and persistent recovery of well-being and of biochemical abnormalities. The patients remained in good health after more than 2 years of follow-up. Our finding of hyperammonemia caused by the lack of thyroid hormones in 3 patients with hypothyroid myopathy appears to be of a certain interest as, to our knowledge, this phenomenon has not been previously described. In conclusion our hypothesis is that increased muscle production of ammonia secondary to the hypothyroid myopathy determined an increased ammonia load, resulting in hyperammonemia. Decreased liver ureagenesis induced by the lack of thyroid hormones also contributed to the hyperammonemia.

Enumeration of CD34+ hematopoietic progenitor cells for clinical transplantation: comparison of three different methods.

Three different methods for determination of CD34+ cells in G-CSF-mobilized peripheral blood were compared. The methods were: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cells enumeration and our own protocol. The procedure we have adopted is essentially a Milan/Mulhouse protocol-derived methodology combined with a multiparametric approach using the PAINT-A-GATE software analysis program. The samples were collected from 70 patients affected by acute leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myeloma and breast cancer who were scheduled to receive autologous PBSC transplantation. PBSC collection was performed following mobilization with subcutaneous G-CSF at 5-10 microg/kg/day. A minimum target of 2 x 10(6)/kg CD34+ cells was considered an acceptable harvest to ensure a safe transplant. On average, three aphereses per patient were performed and a total of 204 apheresis samples were analyzed. Regression analysis of the percentage and absolute number of CD34+ cells, as calculated with each method, achieved an excellent correlation in spite of methodological differences. In fact, both CD34+dim and CD34+CD45- events were included in our gating strategy. In the setting of a triple staining associating CD34, CD38 and CD45, we identified a variable fraction of CD34+CD38+CD45- cells which would be otherwise undetected due to its CD45 negativity. To this end, we used a new technology referred to as laser-scanning cytometry (LSC) which allowed the isolation and morphological identification of CD34+CD45- cells. By comparing CD34+CD45+ and CD34+CD45- cells, we found that they share a common morphology, thus confirming the hypothesis that the latter are to be considered for CD34+ cell calculation. The median number of CD34+ cells/kg, as calculated by the three methods, was: 4.79 x 10(6)/kg (range 1-570) for the Milan/Mulhouse protocol, 3.9 x 10(6)/kg (range 0.8-498) for the ISHAGE one, and 5.17 x 10(6)/kg (range 2-599) for our protocol. The median time to ANC and PLT engraftment was 11 (range 9-24) and 20 (range 10-70) days, respectively. Our protocol achieved the best correlation between CD34+ cells/kg and time to ANC/PLT recovery according to the Spearman's rank test (r = -40 and P < 0. 015 for ANC, r= -46 and P = 0.005 for PLT). We conclude that (1) CD45 does not appear the ideal partner of HPCA-2 for determination of hematopoietic progenitors in mobilized peripheral blood; and (2) for clinical application, a single staining with 8G12 appears simple, reliable and feasible when rigorous procedures for sample preparation and acquisition are followed and an adequate software for multiparametric analysis is available.

The aging process modifies the distensibility of elastic but not muscular arteries.

Aging decreases the distensibility of large elastic arteries; however, the effects of age on the functional parameters of muscular, medium-sized arteries are not well determined. This study evaluated the consequences of aging on the functional parameters of the carotid and radial arteries in normotensive men. A total of 62 elderly subjects (aged 74+/-2 years) were compared with 87 young subjects (aged 35+/-3 years). Internal diameter and intima-media thickness (IMT) were measured by a high-resolution echo-tracking system to calculate distensibility and incremental elastic modulus (Einc). Although in the normal range, systolic and diastolic blood pressure levels were statistically different in the 2 groups at 128+/-19 and 74+/-13 mm Hg versus 121+/-27 and 71+/-18 mm Hg in the young and elderly subjects, respectively (P<0.05). At the carotid artery level, elderly subjects exhibited a greater IMT (742+/-144 versus 469+/-132 microm; P<0.01) and internal diameter (7067+/-828 versus 6062+/-1026 microm; P<0.01) than young subjects; elderly subjects also had lower distensibility (12+/-2 versus 21+/-2 kPa(-1) x 10(-3); P<0.01) and higher Einc (0.9+/-0.2 versus 0.7+/-0.3 kPa x 10(3); P<0.01). At the radial artery level, both IMT (240+/-42 versus 218+/-51 microm; P<0.01) and internal diameter (2685+/-432 versus 2491+/-444 microm; P<0.01) were greater in elderly subjects, but no differences in distensibility and Einc were observed between the 2 groups. All differences remained significant, even after adjusting for mean blood pressure. These results indicate that the increase of the internal diameter and IMT observed during the aging process can have opposite effects on the functional parameters of large elastic or medium-sized muscular arteries.

The carotenoid pigments of a marine Bacillus firmus strain.

As carotenoids have important biological functions, it is important to discover new natural sources of these pigments. The bacterial strains isolated from a sea water rock pool were cultivated on marine agar containing yeast extract and identified by conventional methods. The bacterial pigments were extracted with methanol and analyzed by reversed-phase HPLC with diode array detection. The major pigment of a Bacillus firmus strain was identified as astaxanthin; the results obtained suggest potential use of this bacterium in aquaculture and in pharmaceutical field.

Mechanical removal of airway epithelium disrupts mast cells and releases granules.

Many previous investigators have utilized mechanical rubbing as a method for examining effects of epithelial removal. In the present study, we examined whether this procedure also affects mast cell integrity in the underlying lamina propria. We isolated bronchial rings from six ferrets, and we found that removal of epithelium by rubbing decreased the total number of intact mast cells from 10.0 +/- 1.9 to 2.2 +/- 0.6 (SE) mast cells/mm luminal perimeter (P less than 0.01). In addition, we found a very large number of metachromatic particles that appeared to be mast cell granules unassociated with identifiable mast cells. Their identity was confirmed the presence of free mast cell granules and showed that they contained intact membranes. These effects were not observed when the epithelium was removed by enzymatic digestion, but they were observed after mechanical deformation of the bronchi alone. We suggest that mast cell components released by removing or damaging the epithelium may affect the function of various cells in the airway.

Protease inhibitors potentiate smooth muscle relaxation induced by vasoactive intestinal peptide in isolated human bronchi.

To examine the role of endogenous proteases in limiting the bronchodilating effects of vasoactive intestinal peptide (VIP) in human airway, we studied precontracted bronchial rings from five nonsmokers undergoing heart-lung transplantation for pulmonary hypertension, either primary or secondary to congenital heart disease. The protease inhibitors aprotinin, leupeptin, phosphoramidon, and soybean trypsin inhibitors significantly potentiated the bronchodilator response to VIP. Even in the presence of the four protease inhibitors, VIP-induced bronchodilation reversed spontaneously in some tissues. These studies show that degradation by endogenous airway proteases is an important determinant of the bronchodilating potency of VIP in isolated human airway.

Mast cell tryptase and chymase reverse airway smooth muscle relaxation induced by vasoactive intestinal peptide in the ferret.

Recent evidence suggests that nonadrenergic airway relaxation may be controlled by vasoactive intestinal peptide (VIP). The magnitude and duration of smooth muscle relaxation in response to VIP may be influenced by rates of peptide degradation after release from efferent peptidergic neurons. To explore the potential role of mast cell mediators in modulating neural control of airway tone, we studied the effect of the mast cell proteases tryptase and chymase on airway smooth muscle relaxation induced by VIP in ferret airway. Tracheal rings precontracted by serotonin (10(-6) M) in a muscle bath were relaxed by VIP (10(-7) M). We found that protease-rich supernatant obtained by degranulation of dog mastocytoma cells reversed VIP-induced relaxation, as did highly purified tryptase and chymase incubated with the tracheal rings. Either enzyme completely reversed the effect of VIP, but tryptase was more potent than chymase, paralleling previous test tube observations on the relative rates of VIP cleavage by the two enzymes. Inhibitors of mast cell tryptase and chymase preincubated with the supernatant or with the purified proteases prevented reversal of VIP-induced relaxation. Mast cell proteases did not reverse the tracheal relaxation caused by the nonpeptide adrenergic agonist isoproterenol. These findings show that mast cell proteases tryptase and chymase counteract the smooth muscle relaxant effects of VIP in ferret trachea and suggest a potential role for the mast cell proteases in the modulation of nonadrenergic neural control of airway tone by VIP.

Cardiorespiratory reflexes from muscles during dynamic and static exercise in the dog.

Cardiorespiratory reflex responses during the initial phase of dynamic and static contraction of hindlimb muscles were studied in anesthetized dogs. Muscle contractions were elicited by stimulating the femoral and gastrocnemius nerves at 3 and 100 Hz with the intensity of 2.0-2.5 times the motor threshold for a 20-s period. Rhythmic contractions caused a decrease in arterial pressure (Pa) and heart rate (HR) and increased pulmonary ventilation (VE) by increasing frequency (f) without significantly changing VT. Tetanic contractions provoked an increase in Pa and HR and a hyperpnea resulting from a rise in both f and VT. Similar responses were also obtained in anesthetized dogs with carotid sinuses denervated and cervical vagi cut. The abrupt increase in VE at the start of both types of exercise was not associated with immediate significant decreases in end-tidal CO2 values. These two patterns of cardiocirculatory and respiratory responses were closely similar to those reported in anesthetized rabbits in previous studies. Both patterns of responses were reflexes initiated by activation of muscle receptors verified by interrupting the afferents from the contracting muscles. It is concluded that, during dynamic and static work, two distinct muscular reflex mechanisms might exert their drives, related to the muscular metabolic rate, on the circulatory and respiratory function.