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Biomedical subjects

L Lundblad

Publications and source records attributed to L Lundblad.

At least 19 recordsLinked to original sources
PubMed2004

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.

Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.

Adult↗
PubMed2002

Current perspectives on the treatment of nasal polyposis: a Swedish opinion report.

This Swedish study group has examined the current knowledge of nasal polyposis with emphasis on different treatment modalities. Polyposis is a multifactorial disease that exists for decades in the majority of cases. Different types of treatment must be considered, focusing on the underlying disease. However, as we only know the specific origin of polyposis in a minority of cases, treatment is usually symptomatic. When making a thorough evaluation of different treatment strategies, it is obvious that there is a real need for more controlled treatment studies which would make the scientific ground more stable when it comes to suggesting medical, surgical or combined treatments.

Administration, Intranasal↗
PubMed2001

A randomized controlled study evaluating medical treatment versus surgical treatment in addition to medical treatment of nasal polyposis.

BACKGROUND: Controlled prospective studies are needed to determine whether surgical treatment in fact has an effect additive to that of medical treatment of nasal polyposis. OBJECTIVE: We sought to compare the effect of medical treatment versus combined surgical and medical treatment on olfaction, polyp score, and symptoms in nasal polyposis. METHODS: Thirty-two patients with nasal polyposis and symmetrical nasal airways were randomized to unilateral endoscopic sinus surgery after pretreatment with oral prednisolone for 10 days and local nasal budesonide bilaterally for 1 month. Postoperatively, patients were given local nasal steroids (budesonide). Patients were evaluated with nasal endoscopy, symptom scores, and olfactory thresholds. They were followed for 12 months. RESULTS: The sense of smell was improved by the combination of local and oral steroids. Surgery had no additional effect. Symptom scores improved significantly with medical treatment alone, but surgery had additional beneficial effects on nasal obstruction and secretion. After surgery, the polyp score decreased significantly on the operated side but remained the same on the unoperated side. Twenty-five percent of the patients were willing to undergo an operation also on the unoperated side at the end of the study. CONCLUSIONS: Medical treatment seems to be sufficient to treat most symptoms of nasal polyposis. When hyposmia is the primary symptom, no additional benefit seems to be gained from surgical treatment. If nasal obstruction is the main problem after steroid treatment, surgical treatment is indicated. Selection of those who will benefit from surgery should be based on the patient's symptoms and not on the examiner's polyp score.

Budesonide↗
PubMed2001

Mometasone furoate nasal spray in the treatment of perennial non-allergic rhinitis: a nordic, multicenter, randomized, double-blind, placebo-controlled study.

In order to evaluate the efficacy and safety of mometasone furoate nasal spray (MFNS) in patients with perennial non-allergic rhinitis (PNAR) a phase III, double-blind, randomized, placebo-controlled, Nordic multicenter study was performed at 16 sites (7 in Sweden, 3 in Denmark, 3 in Finland and 3 in Norway). A total of 329 patients (age 18-82 years) with a mean duration of PNAR of 9 years were included in the study. The total duration of the study was 11 weeks: 2 weeks of screening, 6 weeks of treatment and 3 weeks of follow-up. Inclusion criteria were unspecific rhinitis symptoms and exclusion criteria were a positive skin prick test as well as intolerance to aspirin or non-steroidal anti-inflammatory drugs. Endoscopy was performed to exclude patients with structural anomalies and nasal polyps. The primary efficacy variable was the subject's total overall evaluation. In the intention-to-treat (ITT) group of patients (n = 329) the improvement rates were 56% (MFNS) and 49% (placebo). In the per-protocol (PP) group (n = 251) the corresponding figures were 58% and 47%. Stratifying for groups of patients having moderate symptoms, the results were 54% vs 43% in the ITT group and 56% vs 41% in the PP group. The therapeutic response showed greater improvement in total nasal score as recorded by the investigator in the groups treated with MFNS as compared to the placebo group (p = 0.09 [PP], p = 0.14 [ITT]). Adverse events occurred during the study, upper respiratory tract infections and headache being the most frequently reported, but there was no statistically significant difference between MFNS and placebo. The results of this study indicate that MFNS is a safe and effective treatment for patients with PNAR.

Administration, Intranasal↗
PubMed2000

Results of transantral orbital decompression in patients with thyroid-associated ophthalmopathy.

PURPOSE: To present the results of orbital decompression in patients with thyroid-associated ophthalmopathy (TAO). METHODS: Transantral orbital decompression was performed in 63 patients with TAO. In 40 patients (63%) the operation was made because of progressive ophthalmopathy not responding to medical therapy, and in 23 patients (37%) the operation was made for rehabilitative reasons. The long-term hypesthesia engaging the infraorbital nerve was assessed with a questionnaire using a Visual Analogue Scale (VAS). RESULTS: The mean proptosis reduction was 3.2 mm (range 0-8 mm). Twenty-one patients had impaired visual acuity preoperatively, and 20 improved. Altogether 30 patients (40%) had worsened ocular motility postoperatively. Forty-three patients did not have diplopia in the primary position preoperatively, and new diplopia developed in 22 of these (51%). Hypesthesia in the infraorbital nerve area was reported for half of the operated sides, but was a major cause of distress (VAS-scoring >5) to eleven patients. CONCLUSIONS: Transantral orbital decompression is indicated in patients with progressive TAO or in patients with prominent exophthalmos, and results in a good proptosis reduction, but the risk of postoperative diplopia is significant. Postoperative hypesthesia is common but often not a major problem.

Adolescent↗
PubMed1998

Ventilator-associated sinusitis: antroscopic findings and bacteriology when excluding contaminants.

The objective of this study was to investigate maxillary sinus infectious or inflammatory disease in long-term mechanically ventilated patients, using a prospective case series design. The subjects were 33 critically ill patients receiving ventilator treatment for more than 7 days, in the general and neurosurgical intensive care units of a tertiary care hospital. Bilateral antroscopies were performed, and antral secretion and mucosal samples were collected for bacterial culturing. Different stages of inflammatory disease were found in 85% of the antra. Infectious sinusitis was diagnosed in 6%, with a predominance of mixed anaerobic infections. Monoisolates of anaerobic or facultative anaerobic bacteria were found in 5% of the antra without clinical signs of infection. In conclusion, more stringent requirements are needed for the diagnosis of infectious sinusitis in ventilator-treated patients. With improved diagnostic techniques there was a significantly lower frequency of infectious sinusitis than presented in previous reports. The bacteria predominating as infectious agents were different to those in previous reports. Furthermore, reactive inflammatory disease with bacterial colonization occurred.

Bacteria, Anaerobic↗
PubMed1998

Ventilator-associated sinusitis: a review.

A common foreign body of the nose in intensive care, the nasotracheal tube, has for 20 years been cited as a cause of bacterial infection of the paranasal sinus. High frequencies of bacterial culture positivity have occurred in several studies. However, the state of critically ill patients has to be evaluated before conclusions about cause of infection can be made. Nosocomial colonization with intensive care unit flora, in combination with use of antibiotics, precludes the use of procedures that are standard in office practice and microbiological diagnostics. New methods of sampling and quantitative culturing for the specific purpose of intensive care antral diagnostics, in combination with endoscopic inspection, have enlarged our knowledge of sinusitis. Among patients ventilator-treated for > or = 1 week, the occurrence of bacterial sinusitis is < 10%. For 80% of the examined antra there were similar inflammatory reactions without clinical signs of infection. Sporadically in these, cultures of antral specimens were positive for bacteria, which, by definition, would represent colonization.

Anti-Bacterial Agents↗
PubMed1994

Ruthenium red selectively attenuates capsaicin induced vasodilation in pig nasal mucosa.

The effect of ruthenium red, a blocker of transmembrane Ca2+ fluxes, on vasodilation in pig nasal mucosa induced by capsaicin, nicotine, bradykinin or histamine was evaluated in an in vivo preparation. To decrease toxic systemic effects pretreatment with ruthenium red was performed locally, intra-arterially in a nasal artery. Pretreatment with two doses of ruthenium red was evaluated (0.25 and 2.5 mg kg-1). Ruthenium red, in the low dose, resulted in a marked attenuation of the capsaicin-induced nasal vasodilation while the effect on the nicotine-induced vasodilation was not as prominent. Pretreatment with the high dose significantly blocked the vasodilatory effects of capsaicin, nicotine, bradykinin and histamine. Our series indicates that low concentration ruthenium red selectively modulates capsaicin induced vasodilation in pig nasal mucosa in vivo, probably via a direct blocking effect on cation channels opened by capsaicin. A high concentration of ruthenium red may exert a general inhibitory effect on transmembrane Ca2+ transport.

Animals↗
PubMed1993

Mechanical stimulation and capsaicin evoked vasodilation by parasympathetic reflex mechanisms in the pig nasal mucosa.

A model was developed using pentobarbital anesthetized pigs to study bilateral blood flow changes in the nasal mucosa by flow-probes on both sphenopalatine arteries. Unilateral mechanical stimulation of the nasal mucosa for 10s as well as close intra-arterial capsaicin infusion induced bilateral vasodilation. The magnitude of the vasodilator responses were similar on both sides, although the capsaicin effect (maximal increase in arterial blood flow by about 100 ml/min) was larger than that of the mechanical stimulation. Pretreatment with atropine (0.5 mg x kg-1) had no effect on the vascular responses to capsaicin or mechanical stimulation. However, when the pigs were pretreated with the ganglionic nicotinic receptor blocking agent, chlorisondamine (3 mg x kg-1), the vasodilatory responses to mechanical stimulation were abolished and the responses to capsaicin infusion markedly reduced (90-95%). These data indicate that unilateral mechanical stimulation as well as capsaicin infusion evoke bilateral nasal vasodilation which is probably mediated via a central reflex arch with a parasympathetic non-cholinergic final step.

Animals↗
PubMed1992

Effects of acute and long-term atropine treatment on levels, release and response to VIP and PHI in the submandibular gland of cat and rat.

We have studied the effects of acute and long-term treatment of cats and rats with atropine on the levels, release and effects of two peptides, vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), that probably co-exist with acetylcholine in the parasympathetic nerves supplying the submandibular gland. Atropine treatment (progressively increasing doses from 2 to 15 mg kg-1 injected s.c.) for 14 days did not alter the contents of VIP- or PHI-like immunoreactivity (-IR) in the cat submandibular gland or in three other tissues (nasal mucosa, trachea and tongue). Acute as well as long-term atropine treatment decreased the vasodilation following low-, but not high-, frequency parasympathetic nerve stimulation. During prolonged stimulation (60 min) there was a decreased vasodilatation response following both acute and long-term atropine treatment. The overflow of VIP-IR and PHI-IR following parasympathetic nerve stimulation was markedly increased by acute, but not by long-term atropine treatment. The VIP- or PHI-induced stimulation of cyclic AMP (cAMP) accumulation in the cat submandibular gland was not altered after long-term atropine treatment. Similarly, treatment of male Sprague-Dawley rats with atropine (20 mg kg-1) or imipramine (20 mg kg-1) for 14 days did not alter the sensitivity to VIP or to PHI of cAMP accumulation in the submandibular gland, nor was there any change in VIP-IR or PHI-IR content. In conclusion, although atropine treatment causes an acute increase in the overflow of VIP and PHI evoked by parasympathetic nerve stimulation, there is no depletion of peptide stores upon long-term treatment, nor is there any change in the effect of exogenous VIP and PHI on cAMP-accumulation.

Adenylyl Cyclases↗
PubMed1989

Tachykinins and calcitonin gene-related peptide: co-existence in sensory nerves of the nasal mucosa and effects on blood flow.

The presence and co-existence of calcitonin gene-related peptide (CGRP)- and substance P (SP)-like immunoreactivity (-LI) in sensory neurons of the nasal mucosa and trigeminal ganglion in several vertebrate species, including man, were established using immunohistochemistry. In the nasal mucosa the CGRP- and SP-immunoreactive (IR) nerve fibers were localized within the epithelium, around arteries, arterioles, venules, venous sinusoids and close to exocrine elements, mainly ducts. Double-staining experiments revealed that the CGRP-LI-containing nerve profiles and cell bodies also contained SP-LI. In the pig, CGRP- and SP-IR fibers were also detected in the maxillary portion of the trigeminal nerve and around the sphenopalatine artery and vein, as well as around the nasal dorsal vein. The nasal mucosal content of CGRP-LI, as determined by radioimmunoassay, was almost 5-fold higher in the pig and guinea pig compared to man. The nasal CGRP-IR nerves disappeared after capsaicin pretreatment in the guinea pig. In the cat, local intra-arterial infusions of capsaicin, SP, neurokinin A (NKA), neuropeptide K (NPK) and CGRP caused a concentration-dependent increase in nasal blood flow. CGRP caused a longer-lasting vasodilatation than the tachykinins. In conclusion, the morphological findings of co-localization of CGRP-LI and SP-LI in capsaicin-sensitive nerve fibers of the nasal mucosa and trigeminal ganglia of different species including man, coupled with the in vivo description of the high vasodilator potency of CGRP and tachykinins, imply co-release of several vasoactive agents upon activation of the nasal sensory nerves. Furthermore, the similarity of the morphological findings among the different species indicates that experimental data from animals may reflect the existence of similar mechanisms in humans.

Adult↗
PubMed1989

Capsaicin and nicotine-sensitive afferent neurones and nasal secretion in healthy human volunteers and in patients with vasomotor rhinitis.

1. Applications of capsaicin, nicotine and methacholine were made locally onto the nasal mucosa in human controls and patients suffering from hyperreactive nasal disorders. Perception of sensation was registered as a sympton score and secretion quantified. The sensory reaction (irritation - pain) to capsaicin was similar in the three groups studied, i.e. controls, a group of patients with the diagnosis of vasomotor rhinitis and a group of patients with increased nasal secretion as the main symptom of the hyperreactive disorder. Nicotine induced only a mild itching sensation in the three groups. However, capsaicin and nicotine challenge caused a significantly larger secretory response in the last group than in the unselected vasomotor rhinitis group and in the control group. 2. Pretreatment with muscarinic receptor antagonists almost completely abolished the secretory response to both capsaicin and nicotine, and blocked methacholine-induced secretion. Furthermore, pretreatment with a combination of local anaesthetic and vasoconstrictor agent abolished the capsaicin-induced irritation, as well as the capsaicin- and nicotine-induced secretion on both the ipsilateral and the contralateral side. Therefore, no clearcut contribution seems to be exerted by locally released peptides from sensory neurones as direct trigger substances for the secretory response to capsaicin. 3. In conclusion, the nasal secretory response, in man, to both capsaicin and nicotine, seems to be mediated via cholinergic parasympathetic reflexes. In patients with hyperreactive non-allergic disorders of the nasal mucosa with rhinorrhea as the main complaint, the enhanced secretion may be due to a hyperreactive efferent cholinergic mechanism rather than hypersensitive irritant receptors on capsaicin- and nicotine-sensitive sensory neurones. Challenge with irritant agents seems a useful test for the evaluation of both afferent and efferent reflexogenic responses in hyperreactive disorders of the nasal mucosa.

Adult↗
PubMed1988

Antiherpesvirus activity and mechanism of action of indolo-(2,3-b)quinoxaline and analogs.

The antiherpesvirus activity of 14 derivatives of indoloquinoxaline was tested. The most active was 2,3-dimethyl(dimethylaminoethyl)5H-indolo-(2,3-b)quinoxaline, also called B-220. The antiherpesvirus mechanism of B-220 was sought. The compound inhibited replication of herpes simplex virus type 1, cytomegalovirus, and varicella-zoster virus in tissue culture at concentrations of 1 to 5 microM, depending on the cell type used for assay and the amount of virus. Cellular toxicity was seen at a concentration of 10 to 30 microM, and antiviral activity in the human bladder cancer and human embryonic lung fibroblast cell lines tested was found at concentrations 3 to 15 times lower than the concentrations causing cellular toxicity. Viral DNA synthesis, as well as production of early and late viral proteins, was inhibited at 0.5 to 4.5 microM B-220, but viral DNA polymerases tested in vitro were not inhibited at these concentrations. There was no interaction with the pyrophosphate analog foscarnet, and no reversal of the antiviral activity of B-220 occurred with naturally occurring nucleosides. We conclude that the antiviral effect depends on the multiplicity of infection and may occur at the level of viral DNA synthesis and that no interference occurs with pyrophosphate analogs or nucleosides. The more potent activity against viral DNA than against cellular DNA may be caused by a true selectivity for herpesvirus DNA or by the higher metabolism of viral DNA in infected cells.

Acyclovir↗
PubMed1988

Cigarette smoke-induced irritation in the airways in relation to peptide-containing, capsaicin-sensitive sensory neurons.

Cigarette smoke-induced irritation of the nasal and tracheal mucosa induces both protective reflexes and vascular reactions (protein extravasation). The vapor phase of the smoke rather than the particulate phase containing nicotine seems to be mainly responsible for these reactions in the guinea pig and rat, and nicotine-free cigarettes also caused marked irritation. The vapor-phase components activate a specific type of sensory nerves, presumably belonging to the C-fibre group, which are sensitive to capsaicin. These nerves contain tachykinins and CGRP in their peripheral branches within the respiratory epithelium, around blood vessels, and in the bronchial smooth muscle layer. Tachykinins and CGRP are released from these sensory nerves upon acute chemical irritation by, for instance, capsaicin. Tachykinins are potent vasodilating agents and induce plasma-protein extravasation and bronchoconstriction, while CGRP mainly evokes vasodilatation. After pretreatment with high doses of capsaicin, tachykinins and CGRP are depleted from the sensory nerves which subsequently degenerate. The irritation in the nasal mucosa and the tracheal protein extravasation induced by cigarette smoke are absent in capsaicin-pretreated animals, while the mechanical sensitivity and efferent nerve function remain. Also the allergic reaction is reduced after capsaicin treatment, indicating that cigarette smoke and the mediators of the allergen response activate a common pathway.

Afferent Pathways↗