Inhalation and peroral mucolytic therapy in mucoviscidosis in children

The paper summarizes the results of clinical studies of 98 children with mucoviscidosis whose age was 7 to 18 years. There is research evidence for possibility and expediency of using new classes of mucolytic agents in the therapy of mucoviscidosis in children. Analysis of the rheological properties of sputum showed the advantage of inhalation route of mucolytics over their oral administration. There is evidence for the advantage of mucosolvan over carbocysteine and unithiol via all routes of administration, the optimal methods of administration and differentiated indications have been developed.     

Alcohol inhalation in asthma therapy

As part of the search for anticomplementary active components from natural products, the anticomplementary properties of methanolic extracts from the flower buds of Magnoliafargesii have been investigated. Bioassay-guided chromatographic separation of the active constituents led to the isolation of compound 1, whose structure was identified by spectroscopic methods to be kaempferol 3-O-beta-D-(6"-O-coumaroyl)glucopyranoside (tiliroside). Tiliroside showed very potent anti-complement activity (IC50=5.4 x 10(-5) M) on the classical pathway of the complement system, even higher than rosmarinic acid, which is a well-known inhibitor against the complement system. On the other hand, the hydrolysates of tiliroside, kaempferol, astragalin and p-coumaric acid showed very weak activity on this system.     

Severe colitis in mucoviscidosis

We report the association of severe indeterminate colitis with cystic fibrosis in a 21 year old woman, with mild pulmonary involvement, and without digestive or pancreatic symptoms or pancreatic enzyme preparation. Ten cases of inflammatory bowel disease associated with a cystic fibrosis have been reported. Most fit with the diagnostic criteria of Crohn's disease. Although this case was compatible with this diagnosis, we have retained the diagnosis of "severe indeterminate colitis" because of the lack of specific histological features of Crohn's disease. The association between inflammatory bowel disease and cystic fibrosis is probably not fortuitous, although the pathophysiological link between the two diseases is unknown.     

Quality assurance in therapy of mucoviscidosis: value of the Bonn patient information system

The purpose of this study was to investigate the role of superoxide anion (02-*) in the regulation of p53 or c-Ha-ras expression and proliferation in the prostate cancer cell line PC3. Cell proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence of O2-*, basic fibroblast growth factor (bFGF) or their combination. p53 or C-Ha-ras expression in the cells treated with O2-* was assayed by fluorescence in situ hybridization (FISH). The proliferation was significantly inhibited by O2-* in a concentration-dependent manner ranging from 9 to 36 micromol/l nicotinamide adenine dinucleotid (NADH) combined with 2-8 micromol/l N-methylphenazonium methyl sulfate (PMS). Enhancement of proliferation by 2 ng/ml bFGF was significantly inhibited by O2-*. Although O2-* was not able to alter c-Ha-ras gene expression, O2-* at the concentrations of 18 micromol/l NADH and 4 micromol/l PMS upregulated the expression of p53. O2-* may modulate proliferation and gene expression in PC3 cells.     

Nitric oxide inhalation therapy for newborn infants

Binding of NO to heavy metal-containing proteins probably accounts for many of its physiologic actions. NO inhalation is a promising new treatment for various disorders of neonates. The therapy is most likely to benefit premature neonates who are hypoxemic despite breathing pure oxygen and those who suffer from impaired carbon dioxide elimination. Newborn infants who have congenital heart disease may benefit from inhaled NO therapy if their disease involves some form of pulmonary venous hypertension or if they have recently undergone surgery involving cardiopulmonary bypass grafting. The use of NO in infants with PPHN might obviate the need for ECMO or other invasive treatment methods. Neonates with CDH seem likely to benefit marginally from NO therapy. Minimizing the toxicities of NO inhalation therapy requires that the physicians understand the nuances of infant care. The therapeutic value of increasing carbon dioxide elimination with NO inhalation warrants further investigation.     

The radon therapy: radon inhalation spa in Kowary

To study the mechanisms of dorsal axis specification, the alteration in dorsal cell fate of cleavage stage blastomeres in axis-respecified Xenopus laevis embryos was investigated. Fertilized eggs were rotated 90 degrees with the sperm entry point up or down with respect to the gravitational field. At the 8-cell stage, blastomeres were injected with the lineage tracers, Texas Red- or FITC-Dextran Amines. The distribution of the labeled progeny was mapped at the tail-bud stages (stages 35-38) and compared with the fate map of an 8-cell embryo raised in a normal orientation. As in the normal embryos, each blastomere in the rotated embryos has a characteristic and predictable cell fate. After 90 degrees rotation the blastomeres in the 8-cell stage embryo roughly switched their position by 90 degrees, but the fate of the blastomeres did not simply show a 90 degrees switch appropriate for their new location. Four types of fate change were observed: (i) the normal fate of the blastomere is conserved with little change; (ii) the normal fate is completely changed and a new fate is adopted according to the blastomere's new position: (iii) the normal fate is completely changed, but the new fate is not appropriate for its new position; and (4) the blastomere partially changed its fate and the new fate is a combination of its original fate and a fate appropriate to its new location. According to the changed fates, the blastomeres that adopt dorsal fates were identified in rotated embryos. This identification of dorsal blastomeres provides basic important information for further study of dorsal signaling in Xenopus embryos.     

Why do adults with mucoviscidosis refuse a medically recommended course of intravenous antibiotic therapy?

OBJECTIVE: To better understand the needs of spouses who provide care to spinal cord injury (SCI) survivors, by comparing their self-perceptions and complaints with those of their partners with disabilities and with those of spouses who do not provide care. DESIGN: Survey, including demographics, health concerns questionnaire, and administration of the Center for Epidemiologic Studies Depression Scale (CES-D), the Perceived Stress Scale (PSS), the Life Satisfaction Index (LSI-Z), and the Quality of Life and Individual Needs Questionnaire. SETTING: Two British SCI treatment centers, serving a defined population-based catchment area. PARTICIPANTS: One hundred twenty-four spouses of a longitudinally followed sample of SCI survivors, all of whom had been injured 23 or more years when the study was conducted in 1993. OUTCOME MEASURES: Scores on the above standardized tests, and responses to survey questions. RESULTS: Spouses had more depressive affect (p < .001) than their partners with disabilities, as measured by the CES-D. On the PSS, they exhibited no significant differences. Compared with spouses who were not caregivers, the caregiving spouses reported more physical stress (p = .005), emotional stress (p = .011), burnout (p = .007), fatigue (p = .002), and anger and resentment (p = .029). On the CES-D, they had more symptoms of depressive affect (p = .004) and somatic depression (p = .005). CONCLUSIONS: Spouses of long-term SCI survivors who fulfill a caregiving role report more symptoms of stress and depression than their partners with disabilities and other spouses who are not caregivers.     

Amiloride sensitivity in the neonatal rat.

Amiloride-sensitive sodium (Na) channels in taste buds appear to play a key role in the response to NaCl stimulation, at least in adult rats. The researchers examined whether neonatal rats, which display an exaggerated preference for hypertonic NaCl solutions, lack functional amiloride-sensitive Na channels. NaCl intake was significantly reduced by amiloride pretreatment, but water and ammonium chloride were unaffected. The researchers assessed whether the early appearance of amiloride sensitivity was mediated by effects on chorda tympani (CHT) activity by sectioning the CHT before testing. CHT transection reduced intake of NaCl solutions and eliminated evidence of amiloride sensitivity. Amiloride sensitivity was also assessed by recording of whole-nerve CHT activity at 8 to 11 days of age; the response to NaCl stimulation was significantly suppressed by amiloride. These data indicate that amiloride-sensitive Na channels develop earlier than previously believed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic rhinosinusitis in cystic fibrosis (mucoviscidosis)

The authors present two clinical studies performed in the ENT departments of two Belgian Universities. A total of 248 patients with mucoviscidosis (cystic fibrosis, CF) were assessed by means of nasal endoscopy. One hundred eighteen underwent computed tomography of the paranasal sinuses (CT) and 55 were endoscopically operated. This allowed the observation of different clinical patterns of rhinosinusitis: mucopyosinusitis (pseudomucocele) of the maxillary antrum with bulging of the lateral nasal wall (LNW), nasal polyposis with erosion of the LNW, and chronic purulent rhinosinusitis with an isolated prominent uncinate process. The treatment of those patients could be tailored to the individual clinical pattern. Medical therapy consisted of systemic antibiotics and topical drugs delivered by sprays or by lavages with a nose can. Surgery was mainly aimed at removing the massive polyposis when it interfered with the daily life activities. The use of the endoscope enabled to perform safely more extensive procedures resulting in a lower recurrence rate. In patients with chronic rhinosinusitis without polyposis, yet presenting ostiomeatal obstruction, a limited and more functional endoscopic surgery was indicated in order to restore some drainage and to improve the penetration of topical drugs into the affected sinus. A short addendum presents two studies: one about genetics and the other about prevalence of middle ear disease in CF. The first concluded that no clear correlation was found between DF508 (the most common CF mutation) and nasal polyposis. The second revealed that in contrast with the extremely high prevalence of sinus problems, there was no clear evidence of an increased prevalence of middle ear disease in CF.     

Drug inhalation therapy. Therapy for patients with respiratory disorders

We detected a high number of patients suffering from respiratory ailments which require successive hospital stays due to acute setbacks in their chronic respiratory ailments. The majority of these patients receive outpatient clinic treatment based on use of an inhaler. Given the direct relationship between the correct use of an inhaler and its effectiveness, we designed our project with the goal to discover the adroitness these patients have with an inhaler. The results of our study showed that 67% of the patients tested did not correctly use their inhaler, there by annulling or diminished the effectiveness of its use.     

Amiloride and vertebrate gustatory responses to NaCl

Amiloride at < or = 1 microM may block epithelial Na+ channels without affecting other cellular mechanisms, and attenuates gustatory responses to lingual NaCl from the chorda tympani nerves (CT) of gerbil, hamster, rhesus monkey, and several strains of laboratory rat and mouse, and from glossopharyngeally innervated frog taste-receptor cells; at 5 microM to 50 microM, also from Wistar rat and mongrel dog CT. Affected units responded more to NaCl than to KCl. Suppression of CT responses to KCl, HCl, NH4Cl, or saccharides also occurred in some mammals, but amiloride did not elicit responses. Taste-dependent behaviors towards NaCl or KCl were altered. DBA and 129/J laboratory mice, and mudpuppy, were unaffected by amiloride. In humans, 10 microM amiloride both produced taste reports and reduced total intensity of NaCl and LiCl by 15-20%. NaCl and LiCl sourness, and KCl and QHCl bitterness declined, but saltiness generally did not change. Effects on sweetness were inconsistent. Amiloride-sensitive gustatory mechanisms were prominent in some mammals, were not necessary for responses to NaCl, and were of minor importance for human taste.     

Amiloride increases sodium chloride taste detection threshold in rats.

The epithelial sodium-channel blocker amiloride has been shown to inhibit sodium responses in the 7th cranial nerve of the rat. In the signal detection task used in this study, amiloride (100 μM) treatment raised the NaCl threshold by ～1 log?? unit. The inhibition constant for amiloride was 1μM at 0.013 M NaCl. Because the NaCl intake of adult rats has been shown to be related to the level of dietary NaCl exposure early in development, rats were exposed by way of maternal diet to 1 of 3 diets (0.1% NaCl, n?=?8; 1.0% NaCl, n?=?8; 3.0% NaCl, n?=?9) from conception through weaning, to determine whether this treatment affects taste sensitivity. At Postnatal Day 30, rats were placed on 1.0% NaCl chow. This treatment did not affect NaCl detection or amiloride sensitivity in adulthood. The amiloride-induced shifts in NaCl sensitivity functions imply that the transcellular sodium transduction pathway is necessary for normal NaCl detection in the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pathology and pathogenesis of mucoviscidosis (author''s transl)

The section of the cat's mesotympanum, denuded of mucosa, to Silastic and gelatin film was studied and compared with the contralateral control ear, which was also denuded of mucosa. The ears were studied by horizontal pathological sections taken one, two, four, and six months post-lympanotomy and insertion of either gelatin film or Silastic. The Silastic, gelatin film and control ears were compared for inflammatory reaction, amount of fibrosis, and the quality and quantity of mucosal regeneration. The inflammatory reaction was increased in the ears with Silastic compared with their corresponding control ears or to the ears with gelatin film. The amount of fibrosis and the quality and quantity of mucosal regeneration was essentially the same in the Silastic, gelatin film, and control ears. This study shows that both substances are well tolerated in the middle ear and that neither substance stimulated or inhibited the regrowth of mucosa or fibrous tissue when compared with the control.     

Treatment of lung metastases from malignant melanoma with IL-2 inhalation therapy

Seven patients with pulmonary metastases of malignant melanoma were treated with inhalation therapy with 36 million IU interleukin-2 for six months. Inhalation therapy was combined with four bolus infusions of DTIC at a dose of 850 mg/m2 once every four weeks. Response rates were 71.4% with 2 patients achieving a complete remission (CR), 2 partial remissions (PR), 1 stable disease (SD), and 2 progressing disease (PD). Therapy was well tolerated with low toxicity. Six of the patients developed cough; one patient was slightly feverish. We conclude that inhalation therapy of lung metastases is a promising addition to the therapeutic arsenal against malignant melanoma.     

The comparison of early fluid therapy in extensive flame burns between inhalation and noninhalation injuries

Dopamine hydrochloride bearing positively charged small liposomes was prepared by sonicating the multilamellar vesicles. These vesicles were characterized for their physical attributes (shape, size, charge, drug entrapment efficiency, and drug leakage). The drug release kinetics from the liposomes were also studied and found to be Fickian-type diffusion. In vivo performance of the drug-entrapped liposomes was assessed by periodic measurement of drug- (chlorpromazine) induced catatonia in Sprague-Dowley rats. These results were compared with the plain dopamine HCl and levodopa preparations as well with the marketed formulation of levodopa containing carbidopa (Syndopa). These studies revealed that the dopamine can be effectively delivered to the brain by incorporating it into liposomes, and its degradation in circulation can also be protected. The results of liposomal formulation were found to be superior compared to plain levodopa as well as Syndopa.     

NO inhalation therapy for post-operative pulmonary hypertensive crisis of the case of truncus arteriosus

OBJECTIVE: To test stability of insulin lispro in two insulin infusion systems over 48 h. RESEARCH DESIGN AND METHODS: We used reverse-phase and size-exclusion high-performance liquid chromatography (HPLC) to determine the purity, potency, and degree of polymerization of U100 insulin lispro (Humalog) after 24- and 48-h pump cycles conducted at 37 degrees C in five Disetronic H-TRON V100 and five MiniMed 504 pumps. Pumps were set to deliver a basal rate of 0.5 U/h and 6-U boluses at t = 0, 4, 8, 24, 24.5, 28.5, 32.5, and 48 h during each cycle. The effluent was collected into 1-ml vials, pooled at 24 or 48 h, and stored at 4 degrees C until assay. After each 48-h run period of insulin delivery, assays for potency, polymer, and purity were performed on the pooled samples from each individual cycle. m-cresol content and the pooled reservoir content were assayed in the 48-h pooled samples. RESULTS: Insulin lispro retained full HPLC potency (delta < or = 4%) at 48 h, with no degradation of insulin lispro to des-amidoinsulin forms (24 or 48 h). No increase in pumped insulin polymer concentration was observed following 24 h of pump flow. Nonsignificant increases of < or =0.09% (Disetronic) and < or =0.15% (MiniMed) from initial concentrations of 0.18% (polymer divided by total insulin) were detected in three of five pump cycles at 48 h when compared with 37 degrees C paired controls. Nonsignificant decreases (<5 and 10%, Disetronic and MiniMed, respectively) of m-cresol content occurred in both systems following 48 h storage in each device, but sterility was not compromised by this decrease (initial m-cresol concentration, 3.15 mg/ml). Pump performance was without mechanical or electrical fault throughout the study Basal and bolus insulin delivery was evaluated three times daily and remained as expected. Occlusion of catheters by insulin precipitation did not occur, and no change in pH was observed following delivery. CONCLUSIONS: We conclude that insulin lispro is suitable for prolonged infusion in these two medical devices when syringes and catheters are replaced at 48-h intervals.     

Target-controlled inhalation anesthesia or computer-controlled quantitative inhalation anesthesia

Teniposide (VM26) has been claimed to be active with a moderate toxicity in elderly patients affected by small-cell lung cancer (SCLC). Twenty-two patients with SCLC older than 65 years received VM26 as first-line chemotherapy at a dose of 60 mg/m2 on 5 consecutive days every 3 weeks. Age distribution ranged from 67 to 80 years (median 72 years). Fourteen patients were men and eight were women. Twelve patients had limited disease (LD) and ten extensive disease (ED). One patient (LD) had a complete response, and four (3 LD, 1 ED) achieved a partial response for an overall response rate of 22.7% (95% CI 6-40%). The most frequent toxicity was myelosuppression: 20 and 15% of patients had grade 3 leukopenia and thrombocytopenia, respectively. Our results seem to suggest that VM26 by this schedule is moderately effective in elderly patients with SCLC, and it cannot be recommended as a routine treatment.