Nasal polyp load determines the recovery of olfaction after surgery for chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is typically accompanied by impairment of olfaction. Despite of this, until today the efficacy of endonasal sinus surgery (ESS) in terms of olfactory function is still unclear. So far it is known that patients with nasal polyps are most likely to experience post-operative recovery. Within the present study we investigated the sense of smell and other parameters of impairment in CRS before and after ESS in relation to the degree of nasal polyposis, determined with the nasal endoscopic Lildholdt-score. METHODS: Patients with different degrees of severity of nasal polyposis were included. Olfactory function was assessed for odor thresholds [T], odor discrimination [D] and odor identification [I] and the changes of these parameters were investigated postoperatively. RESULTS: For 72 patients baseline measures were available and in 47 patients, postoperative changes were described. There was a correlation between olfactory scores and nasal anatomy/polyposis scores (Lildholdt scores, Lund-Mackay CT score), rated nasal health, and nasal quality of life (sinonasal outcome test). Three months after surgery the average TDI-Score improved by 3.1 points with 30% of patients showing significant clinical improvement. Patients with severe polyposis (Lildholdt score of 5 or 6) benefited most in terms of olfaction. Other significant prognostic indicators of a postoperative increase of olfactory scores included younger age, low pre-operative TDI-scores and high CT-scores. CONCLUSIONS: This study shows that not only the presence of polyps in CRS, but also the degree of nasal polyposis - measured by a grading system - predicts the results in olfactory test results. Additionally, the degree of recovery of olfaction after ESS seems to be most relevant in patients with high polyp scores.

Impact of anterior skull base fracture on lateralized olfactory function.

BACKGROUND: Data on the impact of anterior skull base fractures (aSBF) on lateralized olfactory function are missing. The goal of the study was to investigate olfactory function in patients with traumatic brain injury (TBI) due to aSBF separately for each side and assess the frequency of lateralized smell impairment. METHODS: Retrospective, single center study of olfactory function in 93 patients with aSBF. Olfactory function was assessed by means of the Sniffin' Sticks test battery for each side of the nose, separately. TBI severity was graded according to the Glasgow Coma Scale. Average time interval between olfactory test and trauma was 6.5 years. General olfactory function was defined as the best side out of both nostrils. RESULTS: A total of 50 patients had unilateral and 43 patients bilateral aSBF. The grade of TBI was inversely correlated with olfactory function. General olfactory function was significantly worse in patients with bilateral aSBF compared to patients with unilateral aSBF. Clinically significant side by side differences in olfactory function were found in 18 and 30% respectively for unilateral and bilateral aSBF. Grade of TBI had no significant impact on side differences. Among patients with unilateral aSBF olfactory function was not significantly different between the fractured and the non-fractured side. CONCLUSION: The severity of TBI and bilateral more than unilateral aSBF results in more impaired olfactory function. Lateralized olfactory deficits were not more frequent in any group, regardless of the fracture type and side.

Comparison of clinical tests of olfactory function.

To assess olfactory function, various measures are used in clinical routine. In this study, the Sniff Magnitude Test (SMT), a test considering the sniff response to an odor, was applied to patients with olfactory dysfunction (n = 49) and to a control group without subjective olfaction disorder (n = 21). For comparison, the validated "Sniffin' Sticks" test battery, a psychophysical olfactory test consisting of tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification was performed. Analyses indicated that the SMT showed significant differences between patients and controls (p = 0.003). Furthermore, results from the SMT and the "Sniffin' Sticks" correlated significantly (p < 0.001). In conclusion, the SMT appears to be a useful addition to the battery of available clinical tests to assess olfactory function.

The effect of a herbal combination of primrose, gentian root, vervain, elder flowers, and sorrel on olfactory function in patients with a sinonasal olfactory dysfunction.

Olfactory dysfunction is a common symptom in patients with inflammation of the nasal mucosa. Among numerous drugs, so far only the use of steroids has been shown to have a positive effect on olfactory function. Therefore the aim of the present study was to investigate whether patients with sinonasal disease would benefit in terms of olfactory function from oral treatment with a herbal drug (combination of primrose, gentian root, vervain, elder flowers, and sorrel: Sinupret(r)) which is commonly used in sinusitis. Olfactory function was tested using a standardised olfactory test kit (`sniffin` sticks`). The drug was applied in a double-blind fashion: after an initial therapy of 7 days of oral prednisolone for all participants with a sinonasal olfactory disease, participants were divided into a placebo- and a verum-group; tests were performed before and after treatment over a 2 months period. Statistical analysis did not reveal any major differences in olfactory function in relation to treatment. Considering that its benefit for the inflammatory component of sinusitis has been shown, the herbal drug may exhibit positive effects on olfactory function in a different setting, e.g., when applied without preceding administration of prednisolone, or when used in patients with certain degrees of rhinosinusitis.

The neural representation of odor is modulated by the presence of a trigeminal stimulus during odor encoding.

OBJECTIVES: Odor perception does not simply consist in hierarchical processing from transduction to a single "true" cerebral representation. Odor sensation may be modulated by available sensory information during encoding. The present study set out to examine whether the presence of a pure trigeminal stimulus during odor encoding may modulate odor perception at both behavioral and cortical levels. METHODS: Participants were tested in a 2-session within-subject design: first, an odor encoding session included a delay conditioning procedure in which relatively selective olfactory stimulants (phenyl ethyl alcohol or vanillin, Conditioned Stimulus+, CS+) were presented either with a pulse of CO(2) (Unconditioned Stimulus, US), or alone (Conditioned Stimulus-, CS-); then, in the second session, both pure odorants (CS+ and CS-) were presented alone. During this second session, olfactory event-related potentials were simultaneously recorded and analyzed at different electrode sites including Cz and Pz (sites known to have maximal amplitudes for trigeminal and olfactory stimuli, respectively). After each trial, subjects were asked to rate odor intensity and hedonics. RESULTS: The results showed that CS+ intensity ratings increased in 8 subjects and decreased in 6. Cortically, a group effect was observed for P2 amplitude, which increased in the "CS+ intensity increase" group vs. the "CS+ intensity decrease" group at Cz (p<0.05) but not at Pz (p>0.05). CONCLUSIONS: This result suggests that the presence of a pure trigeminal stimulus (CO(2)) during odor encoding alters the neural representation of a pure odor. SIGNIFICANCE: The neural representation of odors comprises not only the odor itself but also contextual information (trigeminal in the present case) presented during encoding.

A study on the prognostic significance of qualitative olfactory dysfunction.

We investigated the frequency and prognostic significance of qualitative olfactory dysfunction (parosmia, phantosmia) in a retrospective patient based study. A total of 392 patients with impairment of olfaction were tested at least two times for their olfactory function using the "Sniffin' Sticks". The mean interval between the first and the last test was 11 months. At the first visit 34% of all patients reported parosmia. Parosmia was most frequent in patients with postinfectious olfactory loss (56%), and less frequent in idiopathic, posttraumatic, sinunasal disease with frequencies of 10, 14, and 28%, respectively. In contrast, only 12% of all patients had phantosmias, with no significant differences between the patient groups. Improvement of olfactory function was found in 23% of all patients (n = 90). Pre-existing parosmia or phantosmia had no significant effect on recovery rate. Regarding qualitative olfactory dysfunction, 29% of those patients reporting parosmia reported relief of this symptom after an average of 12 months, whereas 53% of phantosmic patients lost phantosmia during the observation period. Although it has been suggested that olfactory distortion s could be regarded as an indicator of early recovery of decreased olfactory sensitivity, the current data indicate that occurrence of parosmia or phantosmia has little prognostic value. Phantosmia disappears at a faster rate than parosmia. These insights into qualitative olfactory dysfunction are regarded to be significant in the counseling of patients with olfactory loss.

Post-infectious olfactory dysfunction exhibits a seasonal pattern.

HYPOTHESIS: We investigated whether olfactory dysfunction following infections of the upper respiratory tract (post-URTI) has an incidence matching the seasonality of URTIs. STUDY DESIGN: Retrospective study. METHODS: In total, 457 patients (126 male, 331 female) with post-URTI olfactory loss were examined during a 6-year-period (1999-2004). Their records were assessed for age, sex, and time of onset of the disease. The severity of olfactory dysfunction was assessed using the "Sniffin' Sticks" (odour threshold, odour discrimination, and odour identification). RESULTS: Incidence of post-URTI olfactory dysfunction exhibited seasonal fluctuations with deviations from the winter seasonality of URTIs. The overall incidence of the disease differed significantly between months. March (12.7%) and May (12.6%) were the months with the highest incidence of the disease throughout the year. The lowest incidence was observed in September (5.6%). Significant differences were found between these months and months with a high incidence of URTIs. DISCUSSION: The peak incidence of post-URTI olfactory loss in March may be explained by the high incidence of influenza at this time. However, it is unclear why the incidence of the disease presents a second peak in May, when the incidence of respiratory viruses is relatively low. Climate conditions at this time might play a role in the susceptibility of the nasal epithelia towards certain viral infections, e.g. parainfluenza type III. CONCLUSION: Post-URTI olfactory dysfunction exhibits spring seasonality with peaks in March and May and possible causative factors being influenza and parainfluenza viruses (type III), respectively.

Molsidomine.

Molsidomine is an established drug for the treatment of coronary heart disease. It acts via the metabolite SIN-1 through liberation of NO. Experiments have proven the identity of NO and EDRF. Investigation of the molecular mechanism of action of molsidomine/SIN-1 indicate that molecular oxygen initiates NO formation through a one-electron abstraction from the intermediate. Ex vivo experiments in rats and in vitro studies in human coronary arteries showed that marked tolerance is induced with glyceryl trinitrate, whereas prolonged exposure to SIN-1 does not cause tolerance. Responsiveness to SIN-1 is not modified in nitrate-tolerant human arteries. Stimulation of soluble guanylate cyclase underlies the antiaggregatory actions of EDRF. Likewise SIN-1 inhibits platelet aggregation in various models. In dogs and pigs with critical stenosis molsidomine reduced significantly the frequency and the severity of cyclical reductions of coronary blood flow.

Cefodizime, an aminothiazolylcephalosporin. V. Synthesis and structure-activity relationships in the cefodizime series.

The synthesis as well as in vitro antibacterial activity and pharmacokinetic behavior of cefodizime (HR 221, 1a), its analogs and derivatives is described. In this comparison, cefodizime stands out for its balance between its high antibacterial activity, prolonged elimination half-life and high AUC in mice and dogs.

Stereochemistry of the epoxydon group antibiotic G7063-2 isolated from a Streptomyces species HPL Y-25711.

The absolute configuration of the ring system of the antibiotic G7063-2 has been established as being the same as that reported for terreic acid, based on circular dichroism data. During structure elucidation experiments, reaction with ethereal diazomethane gave an adduct whose structure is proposed.

Quantitative Determination of Forskolin by TLC and HPLC.

Thin layer chromatographic (TLC) and high pressure liquid chromatographic (HPLC) methods for quantitative determination of forskolin, a novel positive inotropic, antihypertensive, platelet aggregation inhibitory and adenylate cyclase stimulating agent are described. Both methods are suitable for the routine assay of pharmaceutical preparations containing forskolin. The HPLC method is also efficiently used for the assay of forskolin containing plant materials. A comparative evaluation is made of the two chromatographic methods with a previously reported gas liquid chromatographic method to determine forskolin.

Structure-activity relationships for activation of adenylate cyclase by the diterpene forskolin and its derivatives.

Forskolin (7 beta-acetoxy-8,13-epoxy-1 alpha, 6 beta, 9 alpha-trihydroxylabd-14-en-11-one), a diterpene from the Indian plant Coleus forskohlii, activates cyclic AMP generating systems in a number of mammalian tissues in a rapid and reversible fashion. Derivatives of forskolin have been tested for their ability to stimulate membrane adenylate cyclase from rat brain and rabbit heart, as well as cyclic AMP generation in guinea pig brain vesicular preparations, a model system for intact cells. Derivatives at the 6 beta- and 7 beta-hydroxy functions retain activity, but none have greater activity than that of forskolin. Reduction of the 11-keto function affords an active 11 beta-hydroxy derivative. Reduction of the 14,15-vinyl (alpha) substituent reduces activity, while epoxidation abolishes activity. Derivatization or lack of the 1 alpha- and 9 alpha-hydroxy functions results in a marked reduction in activity, emphasizing the importance of the alpha aspect of the molecule. However, the 1 alpha, 6 beta-di-O-acetyl derivative does retain activity. None of the inactive derivatives, which include the 14,15-epoxy, the 1,9-dideoxy, and the 1,6-diketo derivatives, antagonize the stimulatory effects of forskolin.

Deoxymorphines: role of the phenolic hydroxyl in antinociception and opiate receptor interactions.

Several 3-deoxy opioids and 3,6-dideoxydihydromorphine was synthesized to ascertain the effect of the phenolic hydroxyl group on antinociceptive potency and receptor binding affinity. Catalytic reduction of the 3-tetrazolyl ether derivatives of dihydromorphine provided the entry into the 3-deoxydihydro series. The prototype, 3-deoxymorphine, was prepared by lithium aluminum hydride reduction of 3-deoxy-N-carbethoxymorphinone, obtained via its 7-(phenylseleno) derivative. 3-Deoxydihydromorphinone and 3,6-dideoxydihydromorphine were found to be about as potent as, or more potent than, morphine in standard antiociceptive assays. Each of them, however, was less potent than the comparable 3-hydroxy analogue, and their binding affinity to the opiate receptor was substantially decreased. The epoxy ring in 3.6-dideoxydihydromorphine was found to increase the antinociceptive potency of the compound.

Paradoxical effects of N-cyanoalkyl substituents upon the activities of several classes of opioids.

The pharmacological effect of the N-(beta-cyanoethyl) moiety is dependent on the opioid on which it is substituted. It caused a large increase in antinociceptive potency, in (--)-3-hydroxymorphinan and (--)-normetazocine, as compared with the N-methyl opioid. These cyanoethyl compounds do not substitute for morphine in morphine-dependent monkeys. This moiety also appears to greatly increase the ability of the opiate receptor to differentiate enantiomers. An ca. 100,000-fold difference in binding was noted between the epimeric N-(beta-cyanoethyl)-3-hydroxymorphinans and the normetazocines. The levo enantiomers have little acute toxicity and showed excellent therapeutic ratios. In contrast, the N-(beta-cyanoethyl) moiety on normorphine, norcodeine, and noroxymorphone did not appear to improve their pharmacological properties. Homologous N-cyanoalkyl opioids were less potent antinociceptives.