Altered platelet function associated with the bronchial hyperresponsiveness accompanying nocturnal asthma.

BACKGROUND: Nocturnal awakening is a common feature of bronchial asthma, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether nocturnal awakening is associated with changes in platelet function with the use of a variety of markers of platelet activation. METHODS: Ten patients with a history of nocturnal asthma and 10 age- and sex-matched healthy control subjects were studied at 10:00 PM, 4:00 AM, and 10:00 AM on 2 consecutive days. The following parameters were tested: forced expiratory volume in 1 second (FEV1), log dose of methacholine inducing a 20% fall in FEV1, platelet count and volume, platelet aggregation induced by collagen or activating factor, and plasma and intraplatelet levels of beta-thromboglobulin and platelet factor 4. RESULTS: We have demonstrated that altered platelet function and platelet activation occurs at 4:00 AM in patients with nocturnal asthma and is associated with the maximum increases in bronchial reactivity. Such changes were not observed in 10 control subjects. Platelet dysfunction has been detected as a reduced aggregatory response of platelets to collagen and platelet activating factor such that up to 5 times more platelet activating factor and 1.5 times more collagen were required to elicit a threshold aggregatory response in asthmatic subjects when compared with control subjects; this difference was evident at all time points tested. Furthermore, at 4:00 AM there were significantly lower levels of intraplatelet beta-thromboglobulin corresponding to the maximum reduction in peak expiratory flow and to the maximal increase in bronchial responses to inhaled methacholine. CONCLUSIONS: These results suggest that platelet activation accompanies nocturnal asthma and further suggest that platelets may play a role in this common clinical condition.

Mild prematurity and respiratory functions.

Pulmonary function tests and bronchial reactivity to methacholine (MCH) were measured in 34 randomly selected prematures (21 males, 13 females; mean age 11.6 years; mean gestational age 34.9 weeks; mean birth weight 1980 g) and in 34 siblings (22 males, 12 females; mean age 12.5 years, mean gestational age 39.5 weeks; mean birth weight 3030 g). None had suffered neonatal respiratory distress syndrome or had been artificially ventilated. Prematurely born children had a residual volume (RV) and residual volume/total lung capacity (RV/TLC) significantly (P < 0.01) increased compared to controls, although the mean values of both groups were still within the upper limits of normal. Furthermore, an increase of closing volume/vital capacity and closing capacity/total lung capacity (CC/TLC) was observed in most patients with increased RV and RV/TLC. No significant difference was observed for bronchial responsiveness to MCH between prematurely born and control children (11.8% and 5.9% of hyperreactive subjects, respectively). Maternal smoking during pregnancy was prevalent in prematures with impaired respiratory functions. In conclusion clinically normal children of smoking mothers who have survived prematurity but present some respiratory function impairment compared to their born-at-term siblings, should be fully informed and protected from risk factors for chronic obstructive pulmonary disease (COPD) in adult life.

Fate of human albumin microsphere and spherocyte radioaerosols in the human tracheobronchial tree.

Human albumin microspheres (99mTc-HAM; 7-25 microns) and spherocytes (99mTc-S; 4-4.5 mu) are particles used for lung mucociliary clearance (MCC) measurements. If radiolabelled HAM aerosols are sent through an airway model to a screen, they appear peripherally distributed, whereas S present a more central and homogeneous distribution. The radioscanning evaluation of particle sedimentation in saline-filled tubes shows quite a different behavior pattern for S, HAM, and surfactant-coated HAM (S-C HAM). In these experimental conditions, S-C HAM and HAM floating properties were better than those of S. This could be explained by physical-chemical factors. Looking for the fate of organic particles after inhalation, we performed multiple bronchial biopsies in seven bronchitic patients, 2 h following inhalation of HAM and S. Scanning electron microscopy revealed that most of S was floating on the mucus layer, while HAM appeared deeply imbedded inside the mucus and partially digested. The same study performed on three bronchitic patients after S-C HAM inhalation, shows that S-C HAM float like S. In vitro, the time-course of tryptic digestion is similar for HAM and for S. However, in vivo, the different location of each particle on the bronchial surface might lead to a different digestion by trypsin and by PZ-peptidase, which are dosable in pathologic mucus. In our opinion, if HAM are coated with surfactant, this should improve the mucus-HAM interaction, thus helping to control variability in lung radioaerosol MCC studies.

Results of a multicenter retrospective study on pediatric brain tumors in Italy.

This retrospective study was undertaken to evaluate the clinical characteristics, course and treatment of children (0-14 years of age) diagnosed with a primary CNS tumor during the period 1976-1982 in Italy. Four hundred and sixty-two patients (263 males and 199 females) were followed by 18 various neurosurgical and pediatric oncology centers. The histologic types most frequently reported were: medulloblastoma (23%), astrocytoma (16%), ependymoma (11%) and spongioblastoma (11%). Of the 388 patients who underwent surgery, radical excision was reported in 42%, partial excision in 32%, biopsy only in 6%, and unqualified surgery in 4%; 19% had no surgery. Radiotherapy and chemotherapy combined were administered in 61% of the 143 patients followed at pediatric oncology centers; 19% received radiotherapy alone, 3% chemotherapy alone, and 17% neither treatment. Forty-six percent of the patients were reported alive, 40% dead, and 14% lost to follow-up. Performance status was identified for 62 patients. The investigation revealed marked differences in the therapeutic treatment administered, thus precluding valid data analysis. This emphasizes the need to coordinate efforts among the institutions and the disciplines involved in the treatment of this form of childhood cancer.

Hemostatic changes in children with acute lymphoblastic leukemia treated according to two different L-asparaginase schedules.

Hemostatic changes in 20 children with acute lymphoblastic leukemia (ALL) who were induced with L-asparaginase (L-asp), vincristine (VCR), and prednisone (PDN) (Group A) were prospectively evaluated. These data were compared with those of a previous group of ALL patients who received L-asp as a single agent during consolidation (Group B). In Group A patients, mean plasma antithrombin activity decreased in the first 2 weeks, though not significantly. Relative to pretreatment values, mean fibrinogen concentration diminished particularly by week 3 (p less than 0.001). Activated partial thromboplastin time (APTT) decreased in the last week as well as after cessation of therapy with L-asp (p less than 0.05). Mean platelet count increased significantly by week 3 (p less than 0.05). Thromboelastograms performed in seven patients confirmed the tendency for thrombosis evidenced by a decreased APTT. Patients in Group B (L-asp alone during consolidation) had decreased concentrations of fibrinogen, AT, and Factors IX and X after L-asp therapy. APTT was prolonged. Our data demonstrate that the tendency for thrombosis is the predominant manifestation of L-asp induced coagulopathy, when the drug is associated with VCR and PDN. Thus the risk/benefit ratio for the use of L-asp early in induction in children with low risk ALL needs to be further evaluated.

Effect of N-acetylcysteine in subjects with slow pulmonary mucociliary clearance.

There is significant evidence that in the general population there are subjects either with fast or slow pulmonary mucociliary clearance rates. At the moment we do not know the physiological importance of such finding. Slow clearers should be regarded as a subpopulation at risk for bronchopulmonary diseases. Therefore, it would be of considerable interest if their mucociliary function could be stimulated by drugs for preventive purposes. Twelve apparently healthy subjects with slow mucociliary clearance rate, selected in an epidemiologic survey in a non-smokers population were given 0.6 g oral N-acetylcysteine/day/60 days in a double-blind cross-over randomized study. After treatment their mucociliary clearance rates increased by about 35% as compared with baseline values, and returned to pre-treatment values after the washout period. Subjects were unresponsive to placebo treatment. It would seem that slow clearers are protected against lung aggressions by prevention and/or mucus-active drugs.

Supportive care for children with cancer. Guidelines of the Childrens Cancer Study Group. Use of venous access lines.

The use of central access lines in children with cancer may significantly improve the quality of life of these patients. Indwelling atrial catheters (Broviac and Hickman catheters) seem at present to be the best technique. These catheters are associated with complications, of which infection is the most feared. However, their use allows patients to undergo complex prolonged therapy with less discomfort. These indwelling catheters also provide venous access at all times, which may be lifesaving.

Glucose metabolism in children with acute lymphoblastic leukemia treated according to two different L-asparaginase schedules.

Oral glucose tolerance tests were performed in 47 children with acute lymphoblastic leukemia (ALL), treated according to 2 consecutive protocols. Glucose and insulin values were assessed before and after L-asparaginase (L-asp). 30 children (group A) received L-asp as a single-agent consolidation course, after achieving remission with vincristine (VCR) and prednisone (PDN). Normal insulin and glucose levels were found in all patients before L-asp; 4 children (13%) had a transient impaired glucose tolerance (IGT) after completing L-asp therapy. 17 children (group B) were given L-asp during induction therapy with VCR and PDN, and all achieved complete remission. 5 patients (23%) had IGT, without hypoinsulinemia, before L-asp administration. IGT normalized in 4 patients after L-asp, the other children developed a diabetes mellitus. Only 1 patient, with a normal IGT test before L-asp therapy, showed a transient IGT after L-asp. In patients with ALL, the presence of IGT before treatment may be related to leukemia. The concomitant use of steroids does not influence the incidence of IGT in our series. Our data reveal normal insulinemia in patients with IGT. Thus, the leukemic process itself may play a much more significant role in inducing abnormalities in carbohydrate metabolism.