Right putamen and age are the most discriminant features to diagnose Parkinson's disease by using 123I-FP-CIT brain SPET data by using an artificial neural network classifier, a classification tree (ClT).

OBJECTIVE: The differential diagnosis of Parkinson's disease (PD) and other conditions, such as essential tremor and drug-induced parkinsonian syndrome or normal aging brain, represents a diagnostic challenge. 123I-FP-CIT brain SPET is able to contribute to the differential diagnosis. Semiquantitative analysis of radiopharmaceutical uptake in basal ganglia (caudate nuclei and putamina) is very useful to support the diagnostic process. An artificial neural network classifier using 123I-FP-CIT brain SPET data, a classification tree (CIT), was applied. CIT is an automatic classifier composed of a set of logical rules, organized as a decision tree to produce an optimised threshold based classification of data to provide discriminative cut-off values. We applied a CIT to 123I-FP-CIT brain SPET semiquantitave data, to obtain cut-off values of radiopharmaceutical uptake ratios in caudate nuclei and putamina with the aim to diagnose PD versus other conditions. SUBJECTS AND METHOD: We retrospectively investigated 187 patients undergoing 123I-FP-CIT brain SPET (Millenium VG, G.E.M.S.) with semiquantitative analysis performed with Basal Ganglia (BasGan) V2 software according to EANM guidelines; among them 113 resulted affected by PD (PD group) and 74 (N group) by other non parkinsonian conditions, such as Essential Tremor and drug-induced PD. PD group included 113 subjects (60M and 53F of age: 60-81yrs) having Hoehn and Yahr score (HY): 0.5-1.5; Unified Parkinson Disease Rating Scale (UPDRS) score: 6-38; N group included 74 subjects (36M and 38 F range of age 60-80 yrs). All subjects were clinically followed for at least 6-18 months to confirm the diagnosis. To examinate data obtained by using CIT, for each of the 1,000 experiments carried out, 10% of patients were randomly selected as the CIT training set, while the remaining 90% validated the trained CIT, and the percentage of the validation data correctly classified in the two groups of patients was computed. The expected performance of an "average performance CIT" was evaluated. RESULTS: For CIT, the probability of correct classification in patients with PD was 84.19±11.67% (mean±SD) and in N patients 93.48±6.95%. For CIT, the first decision rule provided a value for the right putamen of 2.32±0.16. This means that patients with right putamen values <2.32 were classified as having PD. Patients with putamen values ≥2.32 underwent further analysis. They were classified as N if the right putamen uptake value was ≥3.02 or if the value for the right putamen was <3.02 and the age was ≥67.5 years. Otherwise the patients were classified as having PD. Other similar rules on the values of both caudate nuclei and left putamen could be used to refine the classification, but in our data analysis of these data did not significantly contribute to the differential diagnosis. This could be due to an increased number of more severe patients with initial prevalence of left clinical symptoms having a worsening in right putamen uptake distribution. CONCLUSION: These results show that CIT was able to accurately classify PD and non-PD patients by means of 123I-FP-CIT brain SPET data and provided also cut-off values able to differentially diagnose these groups of patients. Right putamen uptake values resulted as the most discriminant to correctly classify our patients, probably due to a certain number of subjects with initial prevalence of left clinical symptoms. Finally, the selective evaluation of the group of subjects having putamen values ≥2.32 disclosed that age was a further important feature to classify patients for certain right putamen values.

[Radiometabolic therapy for metastatic thyroid carcinoma: overview of the literature and rational bases for the use of recombinant human TSH]. / La terapia radiometabolica del carcinoma della tiroide metastatico: overview della letteratura e basi razionali all'utilizzo del TSH umano ricombinante.

The established treatment for differentiated thyroid carcinoma (DTC) is founded on total thyroidectomy and subsequent administration of radioiodine (131I) to ablate the thyroid remnant and to treat the metastatic disease. In the case of metastatic or recurrent disease, further cycles of 131I therapy are often necessary. The condition for maximizing the effectiveness of the treatment is to have an adequate stimulation from TSH, which must be >25-30 mIU/L. This elevation is achieved either discontinuing the hormone suppression therapy for an appropriate period, or administering recombinant human TSH (rhTSH). The latter has shown good clinical efficacy in patients with residual thyroid gland and is nowadays commonly employed since it is easy to use and allows to avoid the side effects of hypothyroidism. It thus represents a good alternative to thyroid hormone withdrawal for the remnant ablation, while is still open the question if its efficacy on the management of metastatic disease is superimposable to thyroid hormone withdrawal. To this purpose, a Panel of expert reviewed the literature, assessing the advantages and disadvantages for the patient, as well as the impact in terms of cost and benefit to the National Health Service. The work of the Panel concluded with a proposal for the use of rhTSH in selected patients with metastatic DTC, in which is considered the efficacy and safety of the product and is examined its use in terms of costs; this proposal was accepted by the Italian Drug Agency resulting in an update of the indications for rhTSH.

Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC).

BACKGROUND: amyloid-PET reading has been classically implemented as a binary assessment, although the clinical experience has shown that the number of borderline cases is non negligible not only in epidemiological studies of asymptomatic subjects but also in naturalistic groups of symptomatic patients attending memory clinics. In this work we develop a model to compare and integrate visual reading with two independent semi-quantification methods in order to obtain a tracer-independent multi-parametric evaluation. METHODS: We retrospectively enrolled three cohorts of cognitively impaired patients submitted to 18F-florbetaben (53 subjects), 18F-flutemetamol (62 subjects), 18F-florbetapir (60 subjects) PET/CT respectively, in 6 European centres belonging to the EADC. The 175 scans were visually classified as positive/negative following approved criteria and further classified with a 5-step grading as negative, mild negative, borderline, mild positive, positive by 5 independent readers, blind to clinical data. Scan quality was also visually assessed and recorded. Semi-quantification was based on two quantifiers: the standardized uptake value (SUVr) and the ELBA method. We used a sigmoid model to relate the grading with the quantifiers. We measured the readers accord and inconsistencies in the visual assessment as well as the relationship between discrepancies on the grading and semi-quantifications. CONCLUSION: It is possible to construct a map between different tracers and different quantification methods without resorting to ad-hoc acquired cases. We used a 5-level visual scale which, together with a mathematical model, delivered cut-offs and transition regions on tracers that are (largely) independent from the population. All fluorinated tracers appeared to have the same contrast and discrimination ability with respect to the negative-to-positive grading. We validated the integration of both visual reading and different quantifiers in a more robust framework thus bridging the gap between a binary and a user-independent continuous scale.

Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience.

PURPOSE AND PATIENTS: The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11-87) with differentiated thyroid carcinoma (DTC). RESULTS: Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (p < 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04; p = 0.04), localization of BM to cervical spine (HR 3.89; p = 0.01), and lack of avid RAI uptake (HR 2.66; p = 0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97; p = 0.006) and localization of BM to the hip (HR 3.86; p = 0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10; p = 0.02), whereas no significant effects were induced by bone-active drugs (p = 0.36), external radiotherapy (p = 0.54), and surgery (p = 0.43) of BM. CONCLUSIONS: SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.

Buprenorphine vs. morphine via the epidural route: a controlled comparative clinical study of respiratory effects and analgesic activity.

Twelve patients with intense or very intense pain of the non-incident type, secondary to neoplasia, were divided at random into two groups and treated with an epidural dose of 3 mg of morphine in 10 ml of glucose solution (6 patients = group M) or with 0.3 mg of buprenorphine in the same vehicle (6 patients = group B). None of the patients had previously been treated with opioids by any route. After first determining basal values, the following assessments were carried out: (1) evaluation of the analgesic effect of the drugs with checks at 30 min and at 1, 2, 3, 4, 6 and 18 h after administration, using a visual analogue scale, a numerical rating scale and a simple descriptive scale; and (2) evaluation of effects on respiration by means of checks at 30 and 90 min and at 6 and 18 h, on control of breathing indices (P0.1; VE; VA; Ti/Ttot; VT/Ti; RR), gas exchange indices (delta(A-a)O2; VD/VT; pAO2; R) and blood gas and acid-base indices (paO2; paCO2; pH; HCO3-). The data obtained were analyzed statistically using analysis of variance and Student's t test. The study results showed very similar analgesic efficacy for both treatments at a single dosage level of morphine (3 mg) compared to buprenorphine (0.3 mg), which was approximately 3 times greater than an equivalent parenteral dose of morphine (10 mg). Analysis of the results revealed statistically, though not clinically, significant changes in respiratory function indices, only in the buprenorphine-treated group. The effects of buprenorphine on respiratory function, when administered epidurally at the above dosage, are less favourable than those of morphine in the early measurements, probably because of its greater systemic absorption; nevertheless, the risk of delayed respiratory depression appears to be less after buprenorphine than after morphine.

Differentiated thyroid carcinoma in children and adolescents: a 37-year experience in 85 patients.

UNLABELLED: This study reports on 85 differentiated thyroid carcinoma (DTC) (72 papillary, 13 follicular) patients, younger than 18 yr of age at the time of diagnosis, consecutively treated during the period 1958-1995. METHODS: Follow-up (median: 111 mo, range 1-324 mo) consisted of clinical examination, serum thyroglobulin (Tg), 131I whole-body scintigraphy (whole-body scan) and other imaging procedures. RESULTS: Forty-six patients had undergone total thyroidectomy, 38 partial thyroidectomy and 1 thyroid biopsy. In 47 patients, lymph-adenectomy was also performed. Five patients were treated after surgery by external radiotherapy, 59 by 131I therapy and 16 by both modalities. Iodine-131 therapy was successful in ablating thyroid remnants in 35/48 cases, lymph node metastases in 8/11 cases and lung metastases in 12/16 cases. Among the patients with scintigraphic-confirmed disappearance of lung metastases, serum Tg was still detectable in 10 cases, but continued to decrease spontaneously even without further therapeutic doses of 131I. All patients were still alive after a median period of 137 mo (range 5-444 mo). Six patients experienced a recurrence of the disease in the neck. Sixty-seven patients were free of disease, 3 had lymph node metastases, 4 lung metastases and 11 had detectable levels of Tg without demonstrable metastases. No impairment of female fertility or untoward genetic effects were noticed. One male patient, treated with 3.33 GBq of 131I, was infertile due to oligospermia. One case of gastric cancer and one of breast cancer occurred 8 and 19 yr, respectively, after 131I therapy. CONCLUSION: Iodine-131 therapy is highly effective in reducing lung metastases, but undetectable levels of Tg are seldom achieved. Total thyroidectomy and 131I therapy is an effective and safe treatment for the majority of patients with DTC diagnosed in childhood or adolescence.

Assessment of female fertility and carcinogenesis after iodine-131 therapy for differentiated thyroid carcinoma.

UNLABELLED: The aim of this study was to evaluate female fertility, carcinogenic, and genetic effects after treatment with 131I of differentiated thyroid carcinoma. METHODS: A total of 814 females of child-bearing age were studied. The fertility of 627 females who received 131I therapy was compared to 187 untreated females. Birth histories of the children born from these women were registered. The carcinogenic effect was evaluated by comparing the incidence of tumors in 730 patients treated with 131I with an internal control group, as well as with local population incidence. RESULTS: There was no significant difference in the fertility rate, birth weight and prematurity between the two groups. Only one case of a ventricular septal defect was observed in a child born to a women treated with 131I. The overall standardized incidence ratio (SIR) of second tumors was 1.19 (95% CI: 0.76-1.77) in patients treated with 131I. An elevated SIR was registered for salivary gland tumors and melanoma. No case of leukemia was registered. CONCLUSION: The risk of long-term effects of 131I treatment of differentiated thyroid carcinoma is quite low. Iodine-131 may be safely used in treating cases with a high risk of recurrence.

Severe thyrotoxicosis due to functioning pulmonary metastases of well-differentiated thyroid cancer.

We report two cases of thyrotoxicosis resulting from hyperfunctioning lung metastases from differentiated thyroid cancer. In both patients, a simultaneous diagnosis of thyrotoxicosis and metastatic thyroid cancer was made, based on thyroid function tests as well as 131I whole-body scans showing low thyroid uptake of radioiodine and multiple foci of intense 131I uptake in the lungs. After total thyroidectomy (performed in Patient 2 only) and 131I therapy (cumulative dose of 12.3 GBq in Patient 1 and 9.6 GBq in Patient 2), there was a rapid clinical improvement with significant reduction of the pulmonary metastatic disease in both patients: Patient 1 became euthyroid, while Patient 2 became hypothyroid. Analysis of the 54 cases reported in the literature, including the 2 cases described here, shows this to be a very rare cause of thyrotoxicosis and one that can pose serious problems for both the diagnostic evaluation and choice of therapeutic strategy when compared with the much more common nonhyperfunctioning metastases from thyroid cancer. Lesser degrees of thyroid hormone secretion by differentiated thyroid cancer may be detected and exploited diagnostically by the chromatographic analysis of serum for endogenously labeled thyroid hormones after 131I administration.

Nasal-continuous positive airway pressure in the treatment of near-drowning in freshwater.

In patients who have experienced near-drowning, hypoxemia is the major clinical consequence. We report two cases of patients who have experienced near-drowning in freshwater who were successfully treated with nasal-continuous positive airway pressure (N-CPAP) plus oxygen therapy. Both patients presented a radiographic appearance of bilateral pulmonary edema. We suggest the use of N-CPAP as an easier and less costly alternative to tracheal intubation for treating near-drowning in patients who are breathing spontaneously and who have not experienced loss of consciousness.

Influence of autonomic neuropathy of different severities on the hypercapnic drive to breathing in diabetic patients.

To investigate the effects of the autonomic nervous system on control of breathing, the neuromuscular (mouth occlusion pressure at 0.1 s after onset of inspiration [P0.1]) and ventilatory (minute ventilation [VE]) response to progressive hyperoxic hypercapnia was assessed in diabetic patients with autonomic dysfunction of different severity. Eighteen diabetics with autonomic neuropathy, nine with parasympathetic damage (DANp), and nine with parasympathetic and sympathetic damage (DANp+s), as indicated by marked postural hypotension, low increment of diastolic BP during sustained handgrip, and lowest resting catecholamine plasma levels, were studied together with a group of 10 diabetic patients without autonomic neuropathy (D) and a group of 10 normal subjects (C). All subjects had pulmonary function tests, including maximal voluntary ventilation and diffusion of carbon monoxide, measurements of respiratory muscle strength as maximal inspiratory mouth pressure (MIP) and maximal expiratory mouth pressure (MEP), and a CO2 rebreathing test (Read's method). Although in the normal range, lung volumes and FEV1 and forced expiratory flows were lower in the DANp and DANp+s groups than in the D and C groups, MIP and MEP were similar among C and diabetic groups, as well as resting P0.1, VE, tidal volume (VT), and respiratory rate (RR). The slope of the linear relationship between P0.1 and end-tidal PCO2 (PETCO2) was higher in DANp+s (0.63+/-0.07 cm H2O/mm Hg) than in C (0.45+/-0.06 cm H2O/mm Hg; p<0.05) and three times greater in DANp+s than in D (0.26+/-0.03 cm H2O/mm Hg; p<0.001) and DANp (0.24+/-0.03 cm H2O/mm Hg; p<0.001), who in turn showed a lower deltaP0.1/deltaPETCO2 than C. The VE increase with increasing PETCO2 was greater in DANp+s (3.70+/-0.85 L/min/mm Hg) than in DANp (2.13+/-0.20 L/min/mm Hg; p<0.05) and D (2.37+/-0.40 L/min/mm Hg; p=0.07), but not significantly higher from that of C (3.17+/-0.36 L/min/mm Hg). No differences were found for deltaVT/deltaPETCO2 among the groups, whereas the deltaRR/deltaPETCO2 relationship was steeper in DANp+s than in DANp (p<0.05) and D (p=0.055). These data reflect a depressed CO2 response both in D and DANp. The presumable decrease of the sympathetic nerve traffic in DANp+s appears to reverse this abnormality. DANp+s, however, exhibit an enhanced CO2 neuromuscular response even in respect to C, suggesting that the sympathetic nervous system might modulate the output of the respiratory centers to hypercapnic stimulus.

Macrophage activation by N-acetyl-cysteine in COPD patients.

The effect of in vivo and in vitro N-acetylcysteine (NAC) treatment on destructive activity of macrophages against Candida from COPD patients has been evaluated. Patients received NAC (600 mg) or placebo orally 3 times a day for 15 days and bronchoalveolar lavage (BAL) fluid and peripheral blood were collected before and at the conclusion of treatment. In our system, NAC treatment was not able to modulate antifungal activity of alveolar macrophages, peripheral blood monocytes (PBM), and polymorphonuclear leukocytes. On the contrary, in vitro NAC treatment at appropriate doses (10 micrograms/ml) significantly enhanced antifungal activity of PBM from COPD patients. This phenomenon is mediated by augmented phagocytic activity and phagosome-lysosome fusion. The lack of correlation between in vivo and in vitro studies could be ascribed to differences in the intracellular concentration of the drug that in vivo does not reach levels capable of inducing macrophage activation. We speculate that in COPD patients who undergo long-term NAC treatment, appropriate schedules and doses of the drug could augment resistance against microbial infections which are often life-threatening in these patients.

Ventilatory response to exercise in diabetic subjects with autonomic neuropathy.

We have used diabetic autonomic neuropathy as a model of chronic pulmonary denervation to study the ventilatory response to incremental exercise in 20 diabetic subjects, 10 with (Dan+) and 10 without (Dan-) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan- subjects achieved lower O2 consumption and CO2 production (VCO2) than control subjects at peak of exercise, they attained similar values of either minute ventilation (VE) or adjusted ventilation (VE/maximal voluntary ventilation). The increment of respiratory rate with increasing adjusted ventilation was much higher in Dan+ than in Dan- and control subjects (P < 0.05). The slope of the linear VE/VCO2 relationship was 0.032 +/- 0.002, 0.027 +/- 0.001 (P < 0.05), and 0.025 +/- 0.001 (P < 0.001) ml/min in Dan+, Dan-, and control subjects, respectively. Both neuromuscular and ventilatory outputs in relation to increasing VCO2 were progressively higher in Dan+ than in Dan- and control subjects. At peak of exercise, end-tidal PCO2 was much lower in Dan+ (35.9 +/- 1.6 Torr) than in Dan- (42.1 +/- 1.7 Torr; P < 0.02) and control (42.1 +/- 0.9 Torr; P < 0.005) subjects. We conclude that pulmonary autonomic denervation affects ventilatory response to stressful exercise by excessively increasing respiratory rate and alveolar ventilation. Reduced neural inhibitory modulation from sympathetic pulmonary afferents and/or increased chemosensitivity may be responsible for the higher inspiratory output.

Cerebrovascular reactivity and hypercapnic respiratory drive in diabetic autonomic neuropathy.

Because abnormalities in cerebrovascular reactivity (CVR) in subjects with long-term diabetes could partly be ascribed to autonomic neuropathy and related to central chemosensitivity, CVR and the respiratory drive output during progressive hypercapnia were studied in 15 diabetic patients without (DAN-) and 30 with autonomic neuropathy (DAN+), of whom 15 had postural hypotension (PH) (DAN+PH+) and 15 did not (DAN+PH-), and in 15 control (C) subjects. During CO(2) rebreathing, changes in occlusion pressure and minute ventilation were assessed, and seven subjects in each group had simultaneous measurements of the middle cerebral artery mean blood velocity (MCAV) by transcranial Doppler. The respiratory output to CO(2) was greater in DAN+PH+ than in DAN+PH- and DAN- (P < 0.01), whereas a reduced chemosensitivity was found in DAN+PH- (P < 0.05 vs. C). MCAV increased linearly with the end-tidal PCO(2) (PET(CO(2))) in DAN+PH- but less than in C and DAN- (P < 0.01). In contrast, DAN+PH+ showed an exponential increment in MCAV with PET(CO(2)) mainly >55 Torr. Thus CVR was lower in DAN+ than in C at PET(CO(2)) <55 Torr (P < 0.01), whereas it was greater in DAN+PH+ than in DAN+PH- (P < 0.01) and DAN- (P < 0.05) at PET(CO(2)) >55 Torr. CVR and occlusion pressure during hypercapnia were correlated only in DAN+ (r = 0.91, P < 0.001). We conclude that, in diabetic patients with autonomic neuropathy, CVR to CO(2) is reduced or increased according to the severity of dysautonomy and intensity of stimulus and appears to modulate the hypercapnic respiratory drive.

Severe thyrotoxicosis due to hyperfunctioning liver metastasis from follicular carcinoma: treatment with (131)I and interstitial laser ablation.

Liver metastases from differentiated thyroid tumors are unusual clinical findings, and are only rarely hyperfunctioning. We report a case of thyrotoxicosis caused by a huge and surgically unresectable liver metastasis from follicular thyroid cancer, unresponsive to treatment with large doses of thionamides. To avoid the hazardous side effects of (131)I treatment in a severely thyrotoxic patient, a preliminary debulking of the liver mass was performed by means of percutaneous interstitial laser photocoagulation. Three treatments (total energy delivery: 7200 J) were performed under ultrasound guidance, with no serious complications, during a 2-week period. One month later, serum thyroid hormones had decreased, general condition was improved, and magnetic resonance evaluation revealed large and well-defined areas of necrosis of metastatic tissue. During the following 10 months, the patient underwent 3 radioiodine treatments. Eighteen months after diagnosis, thyroid hormones were within normal levels, liver mass decreased, and the clinical condition markedly improved. The combination of percutaneous interstitial laser photocoagulation treatment and radioiodine therapy made possible the effective management of a hyperfunctioning and surgically untreatable liver metastasis from thyroid follicular carcinoma, avoiding the side effects of (131)I therapy in a thyrotoxic patient and increasing the effectiveness of radioiodine-induced neoplastic tissue ablation.

Viral and Mycoplasma pneumoniae pneumonias in school-age children: three-year follow-up of respiratory function.

We studied the evolution of respiratory function during and for 3 years after the acute onset of viral and Mycoplasma pneumoniae pneumonias in 13 school-age children. A mixed type transient ventilatory defect (restrictive and obstructive, but mainly restrictive) with large and small airway involvement was observed during the acute phase of the pneumonias. Residual small airway involvement was found over the next 12 months, but no pulmonary function abnormalities were present after 3 years. At that time, one of the 13 subjects displayed bronchial hyperreactivity to distilled water mist challenge. The authors concluded that viral and Mycoplasma pneumoniae pneumonia in previously healthy school-age children does not cause impaired lung function in later childhood.

Interferon-gamma (r-IFN-gamma) induced activation of alveolar macrophages (AM) from anergic patients with chronic obstructive pulmonary disease (COPD).

Forty-six anergic patients (37 males and 9 females, age range 55-79 yr) were selected from ninety-one patients suffering from COPD due to frequent exacerbations and impaired delayed cutaneous reactivity (43.9%). The phenotype of circulating lymphocytes, their proliferative response to a panel of polyclonal T-cell activators and the candidacidal activity (CA) of circulating PMNs (polymorphonuclear cells) were measured. In 13 patients presenting a defective CA of circulating PMNs, the in vitro response of alveolar macrophage CA to r-IFN-gamma was also determined. We found: 1) a significant reduction in the CL response to PHA in COPD patients vs controls; 2) a low PMN-CA in 23 (57%) COPD patients; 3) a non-significant difference in phenotype analysis in patients and controls; 4) lower CA of AMs in COPD patients than in controls; 5) restoration in vitro of CA by r-IFN-gamma in the group of anergic COPD patients presenting depressed CA. We conclude that a defective cell-mediated immunity could be the basis of the enhanced susceptibility to infectious exacerbations in many COPD patients and that, in vitro, it could be reversed by r-IFN-gamma treatment.

Diurnal change of bronchial caliber and airway responsiveness in asthmatics during long-term treatment with long-acting beta 2-agonist salmeterol.

Measurements of bronchial caliber and airway sensitivity were performed 4 times during the day (at 9, 11, 16, and 22 hr) at basal conditions (baseline), following the first inhalation of 50 micrograms salmeterol (acute) and at the 21st, 90th and 150th day after the initiation of an uninterrupted long-term treatment with inhaled salmeterol (50 micrograms b.i.d., at 10 and 22 hr). In each period of the protective effect was assessed by computing the increase of the methacholine dose able to induce a 20% fall of the forced expiratory volume in the first second (PD20FEV1) in terms of doubling dose (DD), either against the respective 9-hour PD20FEV1 value (DD9hr) or against the corresponding baseline PD20FEV1 value (DDbaseline). After the first dose of salmeterol the forced expiratory volume in the first second (FEV1) increased significantly as compared with the 9-hour FEV1 and the corresponding baseline FEV1 at each observation time (p < 0.01). During regular treatment FEV1 was higher than baseline at the 21st and 90th day at each observation time (p < 0.05), whereas at the 150th day no significant FEV1 increments were observed at 9 hr and 22 hr. The acute protective effect exerted by salmeterol amounted to about 2 DD9hr (p < 0.05) and 2 DDbaseline (p < 0.05) at each observation time. At the 21st, 90th, and 150th day, however, no significant increase of DD9hr was found, although a mild decrease of airway sensitivity of 1 DDbaseline of magnitude was observed for all periods at each observation time. We conclude that in mild to moderate asthma salmeterol appears to rapidly lose its ability to improve bronchial responsiveness while it is effective in maintaining a well-sustained bronchodilation despite a small degree of tachyphylaxis.

The effect of ciprofloxacin on oral contraceptive steroid treatments.

The effect of ciprofloxacin, a new broad-spectrum quinolone derivative, on concomitant oral contraceptive steroids has been studied in a double-blind cross-over placebo-controlled randomized trial. Ten healthy women using long-term oral contraceptive steroids received either ciprofloxacin 500 mg BID or placebo during two consecutive cycles. Therapy was continued for seven days from the first day of contraceptive treatment. FSH, LH and oestradiol blood levels were repeatedly determined to monitor contraceptive steroid efficacy. A seven-day treatment with ciprofloxacin did not affect steroid treatment outcome and appears to be safe in women using this contraceptive method.

PIP: In Italy, health care personnel at the General Hospital in Busto Arsizio randomly assigned 10 healthy women, 22-33 years old, using combined oral contraceptives (OCs) over a long time to either the group receiving 500 mg oral ciprofloxacin twice a day for 7 days for 2 consecutive cycles or to the placebo group. They monitored the women daily and took blood samples on days 7, 9, 14, and 16 of the 2 consecutive cycles. Researchers wanted to determine the interaction between OCs and ciprofloxacin. The volunteers had not taken any drug, other than OCs, in the month before the study. The various OCs consisted of .02-.04 mg ethinyl estradiol and .05-15 mg levonorgestrel, .15 mg desogestrel, or .075 gestodene. None of the women experienced breakthrough bleeding. Ciprofloxacin did not change serum levels of luteinizing hormone, follicle-stimulating hormone, or estradiol (p .05). In fact, the levels for both the ciprofloxacin group and the placebo group were below those levels which signal ovulation. The researchers could not determine the effect of ciprofloxacin on entero-hepatic recirculation of estradiol. These results suggested that ciprofloxacin does not reduce the contraceptive effect of OCs and, therefore, can be safely used to treat infections in women using OCs.

Oral beta 2-selective adrenergic bronchodilators.

Oral beta 2-agonists (carbuterol, pirbuterol, procaterol, bitolterol, clenbuterol) are drugs widely used as bronchodilators. The efficacy and selectivity of bronchodilators drugs depend on their intrinsic pharmacological properties and on the route of administration. The characteristics of the oral route are easy usage, precise dosage and assured effects. Consequently, disadvantages (delayed onset of action, more frequent side-effects) and the indications, (patients with severe chronic airways obstruction, nocturnal asthmatic attacks, and children and elderly subjects) are clearly evident. The most recent beta 2-agonists have an efficient and prolonged bronchodilating action with well-known side-effects. In order to control drug efficiency in a large population and identify type and degree of adverse reactions, a post-marketing surveillance study was programmed for clenbuterol. The results available confirms that long-term treatment with oral clenbuterol is an effective and safe therapeutical approach. During long-term treatment, tachyphylaxis (a diminished responsiveness) develops. This complex biological phenomenon can be studied, in several ways i.e. functional response of target-organ, appropriate biochemical-metabolical indices, and functional evaluation of the cellular beta-receptors in vitro. Also in the light of evaluation of serum levels of cyclic nucleotides (cyclic adenosine and guanosine monophosphates) it appears that the clinical importance of tachyphylaxis is mild and that chronic therapy with beta 2-agonists is safe and effective when used in selected patients.

Acute ventilatory and gas-exchange effects of a new beta-2 agonist, broxaterol, in asthmatics.

The ventilatory and gas-exchange effects of broxaterol, a new selective beta 2-adrenoceptor agonist, were investigated in ten asthmatics following intravenous administration of a single dose of 200 mcg. Broxaterol elicited a prompt and marked bronchodilating effect (increase in forced expiratory volume in one second and specific conductance), maintained at least up to the sixtieth minute. Minute ventilation and the mean expiratory flow did not increase significantly, the pattern of breathing showing a reduction of expiratory time, without modification of inspiratory time. On the other hand, occlusion pressure did not show any significant rise at all times of observation. Furthermore, the partial arterial oxygen and carbon dioxide pressures and alveolar-arterial difference in oxygen and physiological dead space remained unchanged, when measured at 20 min. The results demonstrated that broxaterol was an effective bronchodilating agent, also when rapidly injected, causing a prompt relief of bronchospasm. With respect to other beta 2-adrenoceptor agonists, this compound did not appear to increase minute ventilation or to induce an impairment of ventilation/perfusion ratio, at least after 20 min, when the bronchodilation was still evident. Finally, no side-effects or alterations of heart rate or blood pressure were reported.