Prevention of relapses of nasal polyposis with intranasal triamcinolone acetonide after polyp surgery: a prospective double-blind, placebo-controlled, randomised study with a 9-month follow-up.

OBJECTIVE: To determine whether intranasal triamcinolone acetonide prevents the regrowth of nasal polyps after polyp surgery. STUDY DESIGN: Randomised, double-blind, placebo-controlled, prospective study. SETTING: Helsinki University Central Hospital. PARTICIPANTS: Sixty patients with nasal polyps entered the study. Patients were included upon arrival for elective polyp operations determined according to our standard clinical criteria. The recurrence of nasal polyposis was followed up for 9 months after surgical treatment at 3-month intervals. MAIN OUTCOME MEASURES: Anterior rhinoscopy, nasal endoscopy, olfactory threshold measurement, active anterior rhinomanometry and acoustic rhinometry were performed at every follow-up visit. RESULTS: On the whole, there was a significant inter-group difference in the change in polyp size of acetylsalicylic acid (ASA)-tolerant patients during the follow-up. In patients with acetylsalicylic acid intolerance, there was no inter-group difference (P = 0.28). No significant differences were noted for nasal resistance, nasal cavity volume, sense of smell and nasal symptoms. CONCLUSION: Triamcinolone acetonide prevents regrowth of nasal polyps after polyp surgery in acetylsalicylic acid-tolerant patients, but not in acetylsalicylic acid-intolerant patients.

The electrocardiographic and hemodynamic effect of metohexital and propofol with and without esmolol.

BACKGROUND: Metohexital and propofol are short-acting induction agents, which have a tendency to prolong the QTc interval of the ECG. We studied whether this increase could be prevented by combining a beta-blocking agent, esmolol, with these drugs. Simultaneously, we studied the hemodynamic effects of these combinations. METHODS: In a randomized, double-blind study, 80 ASA I-II young adults were premedicated with oxycodone and atropin and allocated to one of four groups: propofol (P), propofol + esmolol (P + E), metohexital (E) or metohexital + esmolol (M + E). The doses were 2 mg/kg propofol/metohexital and 1 mg/kg esmolol. Alfentanil 15 microg/kg was used in all groups. The hemodynamic parameters were measured non-invasively and the electrocardiographic parameters using the signal processing method. RESULT: The highest QTc values, which often exceeded the normal upper limit of 440 ms, were recorded at the baseline or immediately after the administration of the induction drugs. The intervals were significantly shorter if esmolol was co-administered with either propofol or metohexital. The heart rate increased in the group M and decreased in the group P + E but remained unchanged in the groups P and M + E. Systolic and diastolic arterial pressures decreased during the study in all groups, most prominently in group P + E. CONCLUSIONS: During the anesthesia induction, the QTc interval was significantly shorter when esmolol was co-administered with either propofol or metohexital. The hemodynamic responses were properly controlled with the combination of metohexital and esmolol as well as with propofol alone, but the combination of propofol and esmolol tended to cause hemodynamic depression.

Sense of smell in long-standing nasal polyposis.

An impaired sense of smell is a common complaint in patients with nasal polyposis, and hyposmia is usually attributed to obstruction of the nasal airways. The duration of nasal polyposis and nasal surgery may also affect olfaction. It has been shown that aging and chronic rhinitis both impair olfaction. The aim of our study was to evaluate the sense of smell in patients who had had nasal polyposisfor at least 20 years. The olfactory threshold was assessed with a commercially available odor detection threshold test. The threshold of 19 (46%) of 41 patients was greater than the age-related upper 95% reference limit. In a forward stepwise multiple regression analysis of all the polyposis patients, the degree of opacity of ethmoidal sinuses seen in computed tomography (CT), polyposis visible in anterior rhinoscopy, total nasal resistance, and gender had a significant association with olfactory threshold.

Inflammatory cell and epithelial characteristics of perennial allergic and nonallergic rhinitis with a symptom history of 1 to 3 years' duration.

BACKGROUND: Perennial rhinitis is an inflammatory condition of the mucosal lining of the nose that may be caused by allergic and nonallergic mechanisms. OBJECTIVE: We sought to characterize the cellular pattern and structural changes in the nasal mucous membrane of patients with perennial rhinitis and compare them with those of control subjects. METHODS: Biopsy specimens were obtained from 27 patients with perennial allergic rhinitis (PAR), from 12 patients with perennial nonallergic rhinitis (PNAR) with eosinophils present in the nasal smear, and from 6 control subjects without rhinitis. In 10 of 27 patients with PAR who were also allergic to pollen, biopsy specimens were taken within the respective season (PARseason). In the other 17 patients, the biopsy was taken outside the pollen season (PARoutside season). Inflammatory cells were identified by using mAbs to their unique granular proteins. RESULTS: The characteristic feature of perennial rhinitis was the accumulation of activated (degranulated) mast cells and eosinophils in the nasal mucosa. The tissue eosinophil/neutrophil ratio was higher, and the loss of epithelial integrity was greater in all patient groups compared with the control subjects. The extent of epithelial damage was significantly larger in patients in the PARseason group compared with that in the PARoutside season and PNAR groups, which did not significantly differ from each other in this respect. The number of eosinophils and mast cells was higher in the PNAR group compared with the PAR groups. In all patient groups, the number of eosinophils correlated with the loss of epithelial integrity. The number of mast cells did not correlate with the extent of epithelial damage nor did the number of neutrophils, except in patients in the PARseason group. CONCLUSION: The accumulation of eosinophils and mast cells, as well as loss of epithelial integrity, was characteristic for perennial rhinitis. Loss of epithelial integrity in the nasal mucosa may be a consequence of the activity of accumulated eosinophils.

Trehalose is required for conformational repair of heat-denatured proteins in the yeast endoplasmic reticulum but not for maintenance of membrane traffic functions after severe heat stress.

Saccharomyces cerevisiae cells grown at physiological temperature 24 degrees C require preconditioning at 37 degrees C to acquire tolerance towards brief exposure to 48-50 degrees C. During preconditioning, the cytosolic trehalose content increases remarkably and in the absence of trehalose synthesis yeast cannot acquire thermotolerance. It has been speculated that trehalose protects proteins and membranes under environmental stress conditions, but recently it was shown to assist the Hsp104 chaperone in refolding of heat-damaged proteins in the yeast cytosol. We have demonstrated that heat-denatured proteins residing in the endoplasmic reticulum (ER) also can be refolded once the cells are returned to physiological temperature. Unexpectedly, not only ER chaperones but also the cytosolic Hsp104 chaperone is required for conformational repair events in the ER lumen. Here we show that trehalose facilitates refolding of glycoproteins in the ER after severe heat stress. In the absence of Tps1p, a subunit of trehalose synthase, refolding of heat-damaged glycoproteins to bioactive and secretion-competent forms failed or was retarded. In contrast, membrane traffic operated many hours after severe heat stress even in the absence of the TPS1 gene, demonstrating that trehalose had no role in thermoprotection of membranes engaged in vesicular traffic. However, cytosolic proteins were aggregated and protein synthesis abolished, resulting finally in cell death.

Nasal histamine reactivity; relationships to skin-test responses, allergen provocation and symptom severity in patients with long-continuing allergic rhinitis.

It has been reported that skin-test reactivity and rhinitis symptom severity weaken in the course of time. A corresponding weakening might also be seen in non-specific nasal hyper-reactivity, but the relationships of these responses are poorly understood. Our aim was to measure nasal responsiveness to histamine in a series of patients with long-continuing allergic rhinitis and to compare these measurements with skin test responses, allergen provocation and changes in severity of allergic rhinitis symptoms. A total of 73 patients in whom allergic rhinitis had been verified over 20 years earlier were re-interviewed and re-investigated. Skin prick tests with common allergens were performed and the presence of nasal allergy was confirmed by allergen provocation. Non-specific nasal hyper-reactivity was determined with nasal histamine challenge using four concentrations of histamine phosphate. The response was registered by counting sneezes, recording changes in nasal discharge and mucosal swelling and measuring nasal airway resistance. Sneezing and discharge scores showed that milder non-specific nasal hyper-reactivity was associated with lack of reactivity in skin prick tests and nasal allergen challenge. No association was observed between allergy test results and changes in nasal airway resistance during the histamine provocation. In most patients the symptoms of rhinitis had become milder or disappeared during the follow-up, but the results of the histamine challenge showed no relationship with the changes in symptom severity. In patients with allergic rhinitis, reactivity to histamine is associated with a concomitant change in skin and nasal mucosal reactivity to allergens.

The cytoplasmic chaperone hsp104 is required for conformational repair of heat-denatured proteins in the yeast endoplasmic reticulum.

Severe heat stress causes protein denaturation in various cellular compartments. If Saccharomyces cerevisiae cells grown at 24 degrees C are preconditioned at 37 degrees C, proteins denatured by subsequent exposure to 48-50 degrees C can be renatured when the cells are allowed to recover at 24 degrees C. Conformational repair of vital proteins is essential for survival, because gene expression is transiently blocked after the thermal insult. Refolding of cytoplasmic proteins requires the Hsp104 chaperone, and refolding of lumenal endoplasmic reticulum (ER) proteins requires the Hsp70 homologue Lhs1p. We show here that conformational repair of heat-damaged glycoproteins in the ER of living yeast cells required functional Hsp104. A heterologous enzyme and a number of natural yeast proteins, previously translocated and folded in the ER and thereafter denatured by severe heat stress, failed to be refolded to active and secretion-competent structures in the absence of Hsp104 or when an ATP-binding site of Hsp104 was mutated. During recovery at 24 degrees C, the misfolded proteins persisted in the ER, although the secretory apparatus was fully functional. Hsp104 appears to control conformational repair of heat-damaged proteins even beyond the ER membrane.

Changes in skin and nasal sensitivity to allergens and the course of rhinitis; a long-term follow-up study.

BACKGROUND: Allergic skin test reactivity tends to decrease with aging, but whether the decrease is associated with changes in symptom severity and duration of the disease or determined only by aging, is poorly understood. OBJECTIVE: Our aim was to analyze skin test sensitivity some 20 years after primary testing and to relate possible changes in reactivity to aging, duration of rhinitis, and changes in severity of rhinitis symptoms. METHODS: One hundred and seven rhinitis patients who had been investigated earlier were re-interviewed and their current allergy re-assessed after a follow-up of 23 years. All patients were skin prick tested with 22 to 26 common allergens. The allergic rhinitis status was verified with nasal allergen challenge. RESULTS: Skin test reactivity showed a significant trend decreasing towards older age groups over the period between the two investigations. Rhinitis symptoms tended, on average, to become milder during the follow-up, but an association between skin test reactivity and changes in symptom severity could not be verified. CONCLUSIONS: Rhinitis symptoms tend to become milder and the allergic skin reactivity usually decreases in the long run, but these changes may occur independently of each other. In this study, the change in rhinitis symptom severity seems not to be related to the decrease in skin test reactivity.

Effect of esmolol on the hemodynamic and electrocardiographic changes during laryngomicroscopy under propofol-alfentanil anesthesia.

Laryngomicroscopy is a short-lasting procedure, which causes considerable hemodynamic and ECG changes. Therefore it sets specific demands on anesthetic care. In this double-blind randomized work, we studied hemodynamic and ECG changes in patients during laryngomicroscopy in jet ventilation under propofol-alfentanil anesthesia with and without esmolol, a short-acting beta1-adrenergic receptor blocking agent. Forty ASA class I-II patients were allocated to receive either esmolol 1 mg.kg-1 + 200 micrograms.kg-1.min-1 (the esmolol group) or saline (the control group) (mean age +/- SD 36 +/- 12 yrs in the esmolol group and 39 +/- 9 yrs in the control group). The heart rate and arterial pressure were measured non-invasively and ECG was analyzed with the aid of a microcomputer. In the control group, neither the heart rate nor the QTc interval of the ECG did change significantly when compared with the baseline values. In the presence of esmolol, the heart rate decreased and the QTc interval shortened during the procedure. Arterial pressure increased in the control group, but not in the esmolol group, when compared with the baseline values. No cardiac arrhythmias occurred in either of the groups. On the basis of the present study, propofol-alfentanil anesthesia combined with esmolol is a satisfactory method to meet specific demands of laryngomicroscopy in young and middle-aged ASA I-II patients. However, a combination of propofol and esmolol showed a tendency to decrease both the heart rate and arterial pressure and a caution is necessary when the combination were used in elderly patients.

Effects of four anticholinesterase-anticholinergic combinations and tracheal extubation on QTc interval of the ECG, heart rate and arterial pressure.

BACKGROUND: Imbalance in cardiac sympathetic tone causes prolongation of the QTc interval of the ECG. On the other hand, impairment of the parasympathetic control of the heart rate caused by anticholinesterase-anticholinergic combinations might also affect the cardiac sympathetic tone and hence the QTc interval of the ECG. The main purpose of the present study was to compare the effects of four anticholinesterase-anticholinergic combinations used for the antagonism of the neuromuscular block on the QTc interval of the ECG, heart rate and arterial pressure. METHODS: Eighty-four ASA class I-II patients with a mean age of 32 to 37 yr undergoing otolaryngological surgery were randomly allocated to one of the following groups: neostigmine 40 microg/kg+glycopyrronium 8 microg/kg (Ne-Glyc), neostigmine 40 microg/kg+atropine 20 microg/kg (Ne-Atr), edrophonium 200 microg/kg+atropine 300 microg (Edr-Atr (1)), edrophonium 500 microg/kg+atropine 7 microg/kg (Edr-Atr (2)). QTc interval and heart rate were measured by a signal processing method based on an IBM/PC/xT-compatible microcomputer and arterial pressure with a sphygmomanometer at 1-min intervals up to 10 min after the injection of the drugs and immediately and 2 min after extubation. The ECG, lead II, was continuously recorded. Neuromuscular block was measured by a Datex relaxograph. RESULTS: In all groups, the most pronounced increase in both QTc interval, heart rate and arterial pressure occurred 1 min after the study drugs and immediately after extubation. In all groups, the mean QTc intervals at 1 and 2 min after the study drugs and after extubation were longer than the upper limit of the normal range (440 ms). Junctional rhythm occurred in 1 to 3 patients in all other groups with the exception of the Edr-Atr(1) group in which no cardiac arrhythmias occurred. At 1 min, the heart rate in the Ne-Atr group was at a significantly higher level than that in the Ne-Glyc group. From 3 to 6 min, the heart rate in the Edr-Atr(2) group and at 3 min in the Edr-Atr(1) group was at a lower level than the heart rate in the Ne-Glyc group. CONCLUSIONS: On the basis of the present results, anticholinesterase-anticholinergic combinations should be avoided in patients having a long QT interval syndrome or a prolonged QT interval from other causes. In addition, the cardiovascular stimulation caused by tracheal extubation should also be avoided in these patients.

Sense of smell in allergic and nonallergic rhinitis.

Hyposmia is a fairly common complaint in patients with long-continuing allergic or nonallergic rhinitis. Other factors such as aging, smoking, or nasal surgery may affect olfaction, but these have been little studied in rhinitis-related hyposmia. The purpose of this study was to measure and compare olfactory thresholds in 105 rhinitis patients and 104 healthy controls and to analyze possible relationships between the sense of smell and rhinitis, age, sex, smoking, prick-test results, nasal resistance, and history of nasal or paranasal surgery. The olfactory threshold was assessed with a commercially available kit of squeeze-bottle pairs. The most important variables associated with the sense of smell were determined with stepwise multiple regression analysis, and intergroup differences were assessed with analysis of variance. The reference interval of olfactory thresholds by age was estimated with regression analysis. Nasal resistance was measured by active anterior rhinomanometry. Age and rhinitis were the only variables with significant effect on the olfactory threshold in the whole series. Both the proportion of hyposmic persons and the degree of the impairment of the sense of smell were significantly higher in the rhinitis group than in the control group. The nonallergic patients' sense of smell was poorer than that of seasonal or perennial allergic rhinitis patients. A history of operations for nasal polyposis was associated with hyposmia, but operations for chronic maxillary sinusitis were not. Neither smoking habits nor sex were related to olfactory thresholds. In conclusion, hyposmia in rhinitis patients is partly attributable to age-related changes, but our results indicate that the disease itself impairs the sense of smell.

Sensation of nasal airflow compared with nasal airway resistance in patients with rhinitis.

Over the past few decades there has been some controversy over the relationship between subjective assessment and objective measurement of nasal airway obstruction. To study the hypothesis that there is a close relationship between the two parameters, we analysed changes in nasal patency following histamine challenge. One hundred and two subjects with a history of allergic or non-allergic rhinitis assessed their nasal patency on a visual analogue scale during nasal histamine provocation. Active anterior rhinomanometry was performed immediately after each patient assessment. At all points, significant correlations were observed between subjective and objective assessments of nasal obstruction. Regression analysis also provided strong evidence of a close relationship between the two parameters. We conclude that rhinomanometry can be used as an objective tool in determining nasal patency.

Effect of esmolol on the heart rate, arterial pressure and electrocardiographic changes during laryngomicroscopy.

BACKGROUND: Laryngomicroscopy causes considerable haemodynamic and ECG changes and therefore requires high doses of anaesthetic agents, which prolong recovery. In this double-blind randomized work, we studied the effect of esmolol, a short-acting beta-adrenergic receptor-blocking agent, on haemodynamic and ECG changes during laryngomicroscopy under thiopental-alfentanil-isoflurane-suxamethonium anaesthesia. METHODS: Forty ASA class I-II patients (mean age 43 +/- 11 yr) were allocated to receive either esmolol 1 mg.kg-1 + 200 micrograms.kg-1.min-1 (the esmolol group) or saline (the control group). Heart rate and arterial pressure were measured noninvasively and ECG was analyzed with the aid of a microcomputer. Comparisons between the groups were performed using two-way analysis of variance with repeated measures and the Student's t-test. RESULTS: In the presence of esmolol, neither the heart rate nor the QTc interval of the ECG increased significantly when compared with the baseline values, with the exception that the QTc interval was increased after intubation. The increase in arterial pressure after insertion of the operating laryngoscope was not prevented in esmolol-treated patients. No cardiac arrhythmias occurred in either of the groups. CONCLUSIONS: On the basis of the present study, esmolol-bolus + infusion during alfentanil-isoflurane anaesthesia in healthy, middle-aged patients is a useful treatment in circumstances where an increase of the heart rate, prolongation of the QTc interval and cardiac arrhythmias should be avoided.

Astemizole in combination with pseudoephedrine in the treatment of seasonal allergic rhinitis.

The efficacy and side effects of once-daily astemizole-D, a combination of 10 mg astemizole and 240 mg pseudoephedrine, were compared with those of twice-daily brompheniramine-D, a combination of 12 mg brompheniramine and 50 mg phenylpropanolamine (Lunerin), in 64 patients with seasonal allergic rhinitis caused by birch pollen. Efficacy was monitored by patient's diary scores, investigator assessments of nasal and eye symptoms and need of rescue medication during the 4-week study period. Both astemizole-D and brompheniramine-D reduced nasal and eye symptoms of allergy. There were no significant differences between the treatment groups regarding obstruction, but brompheniramine-D alleviated symptoms of rhinorrhoea and itchy eyes significantly more than astemizole-D. On the other hand, the patients in the brompheniramine-D group reported dry mouth, tiredness and drowsiness more often than those in the astemizole-D group. The results indicate that the two drugs are effective in the treatment of seasonal allergic rhinitis, but astemizole-D is better tolerated than brompheniramine-D.

Long-term clinical course of hypersensitive rhinitis.

Information on the long-term clinical course of hypersensitive rhinitis was collected among 180 patients who had previously participated in an allergological study. The time period between the initial study and the follow-up questionnaire study was about 18.2 years. Of the patients, 72 were men and 108 women, aged 3.6-69.3 years (mean age 28.5 years) at the time of the initial study. Initially, atopic rhinitis had been verified by allergological investigations in 61.7% while 38.3% of the cases had been designated as intrinsic. During the 18-year period symptoms decreased in severity in 37.2% and ceased completely in 27.2%. Total disappearance of symptoms was more frequent in the intrinsic than in the atopic group.

A comparison between intranasal budesonide aerosol and budesonide dry powder in the treatment of hay fever symptoms.

Sixty patients with seasonal allergic rhinitis due to birch pollen were enrolled in an open, randomized parallel group study. Efficacy and side effects were studied after intranasal administration of budesonide given as a freon propellant aerosol or as dry powder with a sniff actuated inhalation device. Medication started a few days before the actual peak pollen season and lasted for three weeks. The dose was 400 micrograms once daily. Efficacy was assessed daily by patient-rated symptoms scores and by nasal peak inspiratory flow measurements at the visits to the clinic. Safety was assessed by monitoring clinical adverse events. No clear changes in nasal symptom scores or nasal peak flow occurred during the pollen season in either treatment group as compared to the pretreatment period, although the pollen season was very difficult in Finland during the study, ad 12000 grains per m3. Substantial or total control of symptoms was achieved in 93% of the patients in the aerosol group and in 79% in the powder group. Side effects were minimal in both groups. We conclude that dry powder administration of budesonide is as effective and well tolerated as the aerosol in the treatment of seasonal allergic rhinitis.