Unique influence of stimulus duration and stimulation site (glabrous vs. hairy skin) on the thermal grill-induced percept.

BACKGROUND: The application to the skin of spatially interlaced innocuous warm (40 °C) and cool (20 °C) thermodes (termed a thermal grill--TG) can produce an unusual thermal percept, but the mechanisms remain unclear. METHODS: We compared the percept quality and intensity over a 120-s period evoked by each of three configurations of a 6-bar thermal stimulator (6 TS): all 40 °C(WARM); all 20 °C(COOL); alternating bars 40/20 °C (TG) at two body sites (forearm and palm). RESULTS: Both unpleasantness and pain were significantly greater for the TG-induced (vs. either COOL- or WARM-induced) percept. Unpleasantness ratings were significantly higher than pain intensity ratings. Several emotional qualitative descriptors were unique to the TG-induced percept. TG palmar (vs. forearm) stimulation produced a more intense percept and was perceived as painful in more subjects. Temporal profiles of intensities of TG-induced percepts differed from those induced by the COOL or WARM thermodes alone. For both unpleasantness and pain, the site differences in the temporal profile were also unique for TG versus the COOL- or WARM-evoked percepts. Qualitative characteristics of the TG-induced percept varied over time and between subjects. CONCLUSIONS: The TG percept intensity and temporal profile were different from those evoked by either of its component parts. The perceived quality is person-specific. These differences suggest that the classic 'TG illusion' results from complex central integration of several types of peripheral afferent inputs activated by the TG. Differing body site-related roles of thermosensory afferents in discrimination versus temperature homeostasis may explain site-related variations in the percept.

Left main bronchus compression as a result of tuberculous lymphnode compression of the right-sided airways with right lung volume loss in children.

RATIONALE: The superior mediastinal space is confined by the sterno-manubrium anteriorly and the vertebral column posterior. An abnormal relationship between the superior mediastinal structures may result in compression of the left main bronchus. In patients with right-sided pneumonectomy an exaggerated compensatory response may lead to stretching and compression of the remainder of the intra-thoracic airway. Lymphobronchial TB mimics pneumonectomy when it causes compression of the bronchus intermedius, between nodal lymphnode groups with resultant volume loss in the right lung and displacement of the mediastinum to the right. The left main bronchus may be at risk of compression due to rotation and displacement of the major vessels. AIM: To report pediatric cases of right-sided lymphobronchial TB with volume loss, demonstrate the use of angle measurements to quantify mediastinal dynamics and support a pathogenetic theory for left main bronchus compression. MATERIALS AND METHODS: CT scans in children with TB and right lung volume loss, were compared retrospectively with controls using angle measurements based on descriptions of the aorta-carinal syndrome and the post-pneumonectomy syndrome. The Mann-Whitney U-test was used to compare groups. RESULTS: The "Pulmonary bifurcation angle" between the main pulmonary arteries reached statistical significance (P = 0.025). The "Pulmonary outflow tract rotation" angle (pulmonary trunk with the mid sagittal plane) approached statistical significance (P = 0.078). The left main bronchus ranged from complete obliteration in two patients to 0.7 cm. In 16 of 30 patients the size was reduced to less than 75% of expected. CONCLUSION: In children with right lung volume loss from TB, the compression of the contralateral bronchus is due to narrowing of the pulmonary artery bifurcation angle as the main trunk rotates towards the midline. This is comparable to the post-pneumonectomy syndrome.

Insect associates of Ceratocystis albifundus and patterns of association in a native savanna ecosystem in South Africa.

Species of Ceratocystis Ellis and Halstead s.l. include important plant pathogens such as C. albifundus Morris, De Beer, and M. J. Wingfield that causes a serious wilt disease of non-native, plantation-grown Acacia mearnsii De Wild. trees in Africa. The aim of this study was to identify the insects associated with C. albifundus in South Africa and to consider the means by which the pathogen spreads. Insects were collected weekly for 77 wk in a native ecosystem using modified pitfall traps. Trapped insects were identified, and fungi were isolated using carrot baiting and by plating them onto malt extract agar. Fungi were identified using morphological characteristics and DNA sequence comparisons. Three different nitidulid (Coleoptera: Nitidulidae) beetles, Brachypeplus depressus Erichson, Carpophilus bisignatus Boheman, and Ca. hemipterus L, were collected, of which the most common were the Carpophilus spp. Two Ceratocystis spp., namely C. albifundus and C. oblonga R. N. Heath and Jolanda Roux, were isolated from all three insect species. Insect numbers and fungal isolates decreased significantly in the colder months of the year. Of the two Ceratocystis spp., C. oblonga was most abundant, occurring on 0.5% of the Carpophilus spp. C. albifundus was isolated from 1.1% of the Brachypeplus individuals and from 0.01% of the Carpophilus individuals. This study presents the first record of insects associated with C. albifundus and C. oblonga and provides an indication of environmental influences on fungal and insect populations, which could contribute to future disease management.

Ceratocystis larium sp. nov., a new species from Styrax benzoin wounds associated with incense harvesting in Indonesia.

Styrax benzoin trees, native to the island Sumatra, Indonesia are wounded to produce resin that is collected and burned as incense. These wounds on trees commonly develop into expanding cankers that lead to tree death. The aim of this study was to consider whether Ophiostomatoid fungi, typically associated with wounds on trees might be associated with resin harvesting on S. benzoin. Samples were collected from the edges of artificially induced wounds, and particularly where cankers and staining of the vascular tissue was evident. Tissue samples were incubated in moist chambers and carrot baiting was also used to detect the presence of Ceratocystis spp. Fruiting structures with morphology typical of species in the C. fimbriata s.l. species complex and species in the anamorph genus Thielaviopsis were found, on both the incubated wood and the carrot baits. DNA sequences were generated for the Internal Transcribed Spacer regions 1 and 2 including the 5.8S rRNA gene, part of the beta-tubulin and the Transcription Elongation Factor 1-alpha gene regions. These data were compared with those of other species in the C. fimbriata s.l. species complex and Thielaviopsis using phylogenetic analysis. Morphology of the isolates in culture as well as phylogenetic inference showed that the Thielaviopsis sp. present on the wounds was T. basicola. The Ceratocystis sp. from S. benzoin represents a new taxon in the C. fimbriata s.l. complex described here as C. larium sp. nov.

Audit of provincial gastroenterology services in the Western Cape.

BACKGROUND: While disorders such as gastro-oesophageal reflux disease, gastrointestinal (GI) cancers and inflammatory bowel disease are prevalent among all racial groups in the Western Cape, there is little knowledge of local GI service provision. The state of equipment, facilities and staffing is largely unrecorded and to date unknown. The aim of this study was to audit the availability of GI facilities in the provincial sector, which provides care for the majority of people in the Western Cape. METHOD: All hospitals in the Western Cape providing endoscopy were evaluated by means of a hands-on audit, to identify available organisational infrastructure. Data including staffing, details and utilisation of existing equipment, maintenance and disinfection techniques and delays in service provision were collected. RESULTS: Over a period of 12 months, 17 Western Cape hospitals were visited: 3 tertiary, 5 regional and 9 district-level institutions. There are currently 89 GI endoscopes in state service, with an average age of 6.1 years (range 1-23 years). While most institutions utilise video endoscopy, in many instances equipment is near the end of its economic life. A total of 26,434 endoscopic procedures were performed over a 12-month period. Overall at least 60% of all adult endoscopy was undertaken at tertiary institutions. The mean delay from consultation until gastroscopy or colonoscopy was 9.25 weeks (range 0.5-28 weeks) and 8 weeks (range 1-20 weeks), respectively. Only 1 tertiary and 1 regional hospital employed fully trained, registered nurses, and the majority of institutions did not conform to internationally accepted standards for the maintenance and disinfection of endoscopic equipment. CONCLUSION: While endoscopy equipment is widely distributed throughout the province, it is evident from this study that services in the Western Cape fall short of international standards, with delays in endoscopic provision, lack of adequate equipment, inadequate scope maintenance and disinfection and a shortage of trained staff. As such, much of the population reliant on state facilities has poor access to GI health care. These deficiencies need to be addressed.

Patients' rights in New Zealand: complaints resolution and quality improvement.

"Patients' rights" has become a familiar catchword in western countries in recent years. In New Zealand the Office of the Health and Disability Commissioner was established in 1994 to promote and protect patients' rights. The Commissioner also facilitates the resolution of complaints relating to the infringement of patients' rights as set out in the Code of Health and Disability Services Consumers' Rights. Victims of medical misadventure in New Zealand are compensated through a no-fault, state-funded rehabilitation and compensation scheme. The regulatory environment is rehabilitative rather than punitive. This framework is consistent with a systems approach to reducing errors and improving patient safety, and the Commissioner seeks to use the resolution of individual complaints as a tool for improving the quality of care throughout the health care system.

A safe area and angle for harvesting autogenous tendons for anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) reconstruction with autogenous semitendinosus and gracilis tendons has become a common surgical procedure. Lower leg paresthesia following injury to the infrapatellar nerve during harvesting of the tendons has been well documented. Few authors have described the position of the infrapatellar nerve on a flexed knee, which is the position used during ACL reconstruction. The purpose of this study was to determine a safe area and angle where an incision could be made for harvesting of the semitendinosus and gracilis tendons, with the knee in flexion. Twenty right cadaver knees and 20 left knees were dissected. Landmarks on the knee were identified, from where the distances to the nerves (infrapatellar and saphenous) were measured with a vernier caliper. A safe area on the right knee was determined to be on the tibial tuberosity plane between 3.7 and 5.5 cm with a safe angle of incision of 51.6 degrees. A safe area on the left knee was determined to be on the tibial tuberosity plane between 3.6 and 4.9 cm with a safe angle of incision of 52.5 degrees. The results may assist orthopedic surgeons performing ACL reconstruction with semitendinosus and gracilis tendons to avoid cutaneous nerve damage and, therefore, patient discomfort.

Pancreatic carcinoma. Diagnostic and prognostic implications of a normal pancreatogram.

BACKGROUND: The aim of this study was to establish the implications of a normal pancreatogram in patients with pancreatic cancer. METHODS: We reviewed all ERCP done at our institution for the period 1983-92 and studied 62 of 727 patients who had a diagnosis of pancreatic (n = 416) or biliary (n = 311) cancer but a normal pancreatic duct. RESULTS: Thirty of the 62 patients had pancreatic cancer. In 15 cases, the ERCP diagnosis was incorrect, and in 19 cases, Santorini's duct was not visualized. Other imaging revealed a pancreatic head mass in 25 patients (2.5->7 cm). Only three patients had resectable tumors; another eight underwent laparotomy. Five had bypass surgery, 10 required biliary stenting, and nine had no treatment. Four patients died in hospital, and eight were lost to follow-up. In the remaining 18 patients, median survival was 7 months (range, 1-30 months). CONCLUSION: A normal pancreatogram does not exclude the diagnosis of pancreatic cancer, nor does it confer a better prognosis.

Effects of pretreatment with dexfenfluramine and fluoxetine on metoclopramide-induced aldosterone secretion in healthy volunteers.

OBJECTIVE: The present placebo-controlled study was designed to compare the effect of acute pretreatment with dexfenfluramine and fluoxetine on the plasma aldosterone response to metoclopramide. STUDY PARTICIPANTS AND DESIGN: Ten healthy ambulatory male volunteers participated. Following a single-blind, randomised design, each volunteer received metoclopramide as an intravenous bolus of 10mg at 0700 hours on each experimental day. Participants were pretreated at 2200 hours the previous evening and 0500 hours in the morning with one of the following: fluoxetine 20mg, dexfenfluramine 30mg, or placebo. RESULTS: In response to metoclopramide administration, the maximum concentration was significantly higher (p = 0.004) than baseline with placebo, fluoxetine and dexfenfluramine. The area under the curve of dexfenfluramine was significantly larger than that with both placebo (p = 0.007) and fluoxetine (p = 0.004), while that of fluoxetine was significantly larger than that of placebo (p = 0.01). CONCLUSION: Acute pretreatment with both dexfenfluramine and fluoxetine caused an enhancement of metoclopramide-induced aldosterone secretion, probably by augmenting serotonergic neurotransmission via serotonin (5-HT)(4) receptors. The plasma aldosterone levels were significantly higher with dexfenfluramine compared with fluoxetine, probably as a result of larger 5-HT concentrations being available for stimulation of glomerulosa cell activity.

Lack of effect of amitriptyline on risperidone pharmacokinetics in schizophrenic patients.

The interaction between plasma concentrations of the tricyclic antidepressant amitriptyline and the metabolism of the new antipsychotic risperidone was studied in 12 patients with chronic schizophrenia. Each patient received 3 mg risperidone twice a day for 28 days. Amitriptyline was coadministered at doses of 50 mg/day on day 15 and 100 mg/day on days 16 to 21. Amitriptyline did not significantly affect the mean plasma concentrations or pharmacokinetics of risperidone in schizophrenic patients or influence the antipsychotic fraction (the total concentration of risperidone and 9-hydroxyrisperidone, its primary and biologically active metabolite). These results suggest that risperidone dose need not be adjusted when coadministered with amitriptyline at doses up to 100 mg/day in schizophrenic patients.

Lack of bioavailability of mebeverine even after pretreatment with pyridostigmine.

OBJECTIVE: After the oral administration of mebeverine to animal or human, measurable concentrations of the drug have never been found in the plasma. The ex vivo hydrolysis of mebeverine can be blocked by esterase inhibitors. In the present study, human volunteers were pretreated with pyridostigmine to attempt to improve the bioavailability of the parent drug. METHODS: Following a single-blind, random design, 12 normal human volunteers received orally either placebo or 60 mg pyridostigmine, followed 2 h later by 405 mg mebeverine. Blood samples were drawn intermittently for 4 h and were spiked immediately with neostigmine in order to block ex vivo hydrolysis. RESULTS: Even after pretreatment with pyridostigmine, the plasma samples failed to reveal detectable concentrations of mebeverine. Pyridostigmine pretreatment mediated a significantly higher peak concentration of veratric acid, the acid moiety resulting from hydrolysis of mebeverine. CONCLUSION: As mebeverine seemingly undergoes complete presystemic hydrolysis, it seems unlikely that the effects of the drug could be mediated centrally. Furthermore, as it is unlikely that sufficient mebeverine traverses the intestine to exert a local effect on the colon (i.e., the time-course of veratric acid plasma levels does not support such a conclusion), the therapeutic effect of the drug, if any, has to be ascribed to an active metabolite. However, the hydrolysis products of mebeverine are not known to be pharmacologically active.

Breakfasts high in protein, fat or carbohydrate: effect on within-day appetite and energy balance.

OBJECTIVE: To compare the effect of isoenergetically-dense, high-protein (HP), high-fat (HF) or high-carbohydrate (HC) breakfasts (at 08.30) on subjective hunger, fullness and appetite (measured hourly on a 100 mm visual analogue scale), macronutrient balance and ad libitum energy intake (EI), at a test meal (13.30) and throughout the rest of the day (until 23.00). DESIGN: Six men each spent 24 h in a whole-body indirect calorimeter on three separate occasions during which they received breakfasts designed to match 75% of BMR and that comprised, on average 3.1 MJ of protein (HP), carbohydrate (HC) or fat (HF), respectively, the remainder being split between the other two macronutrients. Every item of the ad libitum diet comprised 13% protein, 40% fat and 47% carbohydrate by energy, with an energy density of 550 kJ/100 g. RESULTS: Subjectively-rated pleasantness did not differ between the breakfasts, or any of the subsequent ad libitum meals. Subjective hunger was significantly greater during the hours between breakfast and lunch after the HF (26) treatment relative to the HP (18) or HC (18 mm) meals (P < 0.001), although the HP treatment suppressed hunger to a greater extent than the other two treatments over 24 h. However, mean ad libitum lunch intakes were similar at 5.38, 5.30 and 5.18 MJ (NS) on the HP, HC and HF treatments, respectively. After-lunch intakes were also very similar at 6.14, 6.18 and 5.83 MJ (NS). Mean 24-h energy expenditure amounted to 11.12, 11.14 and 10.93 MJ, respectively, producing energy balances of 5.71, 5.83 and 5.04 MJ (NS), respectively. The HP, HF and HC breakfasts led to enhanced P, F and C oxidation, respectively (P < 0.003). CONCLUSIONS: Large HP, HC or HF breakfasts led to detectable changes in hunger that were not of sufficient magnitude to influence lunch-time intake 5 h later, or EI for the rest of the day. A single positive balance of each macronutrient can be buffered by oxidation and storage capacity, without leading to changes in meal-to-meal EI, when subjects feed ad libitum on unfamiliar diets of fixed composition.

Effects of metoclopramide and tropisetron on aldosterone secretion possibly due to agonism and antagonism at the 5-HT4 receptor.

OBJECTIVE: Part of the prokinetic activity of metoclopramide can possibly be ascribed to agonist activity at 5-HT4 receptors. The 5-HT3 antagonist tropisetron is thought to act as an antagonist at 5-HT4 receptors. In the present study aldosterone secretion in response to the administration of these two drugs was explored to examine the role of the 5-HT4 receptor in aldosterone secretion. METHODS: Following a single-blind, random design, ten normal male volunteers received one of the following regimens on three occasions, with at least 2-week intervals: metoclopramide 10 mg i.v.; tropisetron 5 mg by slow i.v.i., or; tropisetron by slow i.v.i., followed by 10 mg metoclopramide i.v. RESULTS: In response to metoclopramide alone the mean plasma aldosterone level rose significantly to 149% of basal level and remained significantly elevated for the next 20 min. With tropisetron alone, there was a significant 37.8% drop at 60 min and the aldosterone levels remained low for the duration of the experiment. Metoclopramide reversed the decline mediated by tropisetron significantly at 30 and 90 min. Aldosterone levels after the latter regimen also did not differ significantly from baseline at any time period. CONCLUSION: These results would suggest the existence of a tonic stimulatory influence of 5-HT via 5-HT4 receptors on aldosterone secretion, which could be augmented by metoclopramide and blocked by tropisetron. However, the effect of tropisetron per se should be interpreted with caution given the lack of a saline group.

The proportional cumulative area under the curve of paracetamol used as an index of gastric emptying in diabetic patients with symptoms of gastroparesis.

1. The foreshortened 2 h method of measuring liquid gastric emptying (i.e. the proportional cumulative area under the curve of paracetamol) was utilized in diabetic patients in order to detect both gastroparesis and the influence of metoclopramide, a known prokinetic drug, on this condition. 2. Metoclopramide, 10 mg intravenously, caused a significant increase in the median PCAUC from 20 min onwards. 3. In this study delayed gastric emptying was defined as a %PCAUC without pretreatment lower than the 5% percentile at 40, 60 and 90 min for normal volunteers. According to this criterion seven of the 10 patients with clinical symptoms of gastroparesis and/or peripheral neuropathy had delayed gastric emptying. 4. The PCAUC method would therefore seem to be a reliable model for investigating gastric emptying in diabetics and the effects of various prokinetic drugs on this condition.

A noninvasive evaluation of baroreceptor sensitivity with the Valsalva maneuver and phenylephrine methods.

In a double-blind crossover study, we compared baroreceptor sensitivity (BS) and latency, derived from the phenylephrine method with BS and latency derived from phase IV of the Valsalva maneuver (VM), using the Finapres, a noninvasive blood pressure monitor. Ten healthy volunteers were enrolled in the study and BS was determined with placebo, atropine (0.03 mg/kg) and atenolol (10 mg) and was expressed as the linear relation between the change in RR interval following the blood pressure rise induced by either phenylephrine or phase IV of the VM (i.e., after cessation of straining). Baseline baroreceptor sensitivity (p<0.001) and baroreceptor sensitivity in the presence of atropine (p<0.02) was smaller with the VM but no differences in baroreceptor sensitivity between the two methods were evident after atenolol. Although no linearity existed between the two methods under any of the experimental conditions, baroreceptor sensitivity in the presence of atropine was significantly smaller (p<0.01)(and latency delayed (p<0.08)) compared to atenolol-induced changes with both methods. We found excellent correlation between baroreceptor sensitivity derived from the ECG tracing and Finapres recorded beat-to-beat pulse intervals (p<0.001; r>0.8, under all conditions) although the correlation after atropine was not as close (p<0.01; r=0.7). The smaller baroreceptor sensitivity induced by the Valsalva maneuver with placebo and atropine, but not with atenolol, suggests a parasympathetically influenced vasodilation, and sympathetically medicated tachycardia during phase IV of the VM.

The influence of betahistine on the dynamics of the cutaneous hypersensitivity reaction in patients with grass pollen allergy.

Histamine has been well documented as an immune modulator, but the dynamics of a number of histamine receptor agonists and antagonists have not been similarly established. The aim of this study was to determine the effect of betahistine (an H3-receptor blocker with partial H1- and H2-agonism) on the dynamics of the cutaneous hypersensitivity reaction. The skin blister technique was used to collect inflammatory cells after intradermal (i.d.) administration of grass pollen antigen, histamine and betahistine to 11 atopic volunteers. In this open, cross-over study, volunteers were randomly allocated to five treatment protocols i.e. (a) histamine 1 microgram i.d.; (b) betahistine 57, 114 and 285 micrograms i.d.; (c) i.d. grass pollen antigen; (d) (c) plus oral betahistine; (e) (c) plus oral betahistine, cetirizine, (H1-blocker) and cimetidine (H2-blocker). Blister fluid containing cells were collected on microscope slides at 6 and 24 h after i.d. injections. The areas of the wheal and flare and of induration were measured, respectively, at 0.25, and, 1, 6 and 24 h. Combined oral therapy with cetirizine, cimetidine and betahistine reduced the area of grass pollen-induced induration significantly at all time periods, but caused a significant increase in eosinophil and neutrophil vacuolisation during the late phase reaction. This did not occur with orally administered betahistine alone. Intradermal betahistine induced significantly more neutrophil and eosinophil vacuolization than histamine and, in contrast to the latter, also mediated a concentration-dependent late phase induration. The results of this study suggest that the H3-receptor regulates a feedback system in conjunction with that previously proven for the H2-receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

The countering of diazoxide-induced vasodilatation by tenoxicam in normal volunteers.

The effect of the nonsteroidal anti-inflammatory drug, tenoxicam, on diazoxide-induced lowering of standing diastolic blood pressure was explored in 10 normal volunteers. With diazoxide there was a significant fall in the 5-min standing diastolic pressure, i.e. a median drop of 15.5, 11.0, 9.5 and 7.0 mm Hg at 10, 35, 75 and 105 min, respectively, but with the tenoxicam-diazoxide regimen this pressure did not differ significantly from baseline at any time point. Tenoxicam did not modify the diazoxide-induced changes in blood glucose and plasma insulin. It may be that prostaglandins normally contribute to the lowering of peripheral vascular resistance, or that acutely-administered diazoxide enhances the release of vasodilatory prostaglandins.

Effect of longterm cetirizine treatment on the cutaneous hypersensitivity reaction in patients with grass pollen allergy.

In short-term studies cetirizine effectively reduces the early and late phases of the cutaneous hypersensitivity reaction. The aim of this study was to determine its long-term effects on both the vascular and cellular components of the reaction. The skin blister technique was used to collect inflammatory cells after intradermal administration of grass pollen antigen to 10 atopic volunteers. They were treated for 3 months with 10 mg cetirizine twice daily. Tests were done at baseline, before, and 7, 30 and 90 days after initiation of treatment. Blister fluid containing cells was collected on microscope slides at 6 and 24 hours. The area of induration was measured at 0.25, 1, 6, 10 and 24 h. Cetirizine significantly reduced the peripheral blood eosinophil count at 30 and 90 days (75% and 40% reduction respectively); there was no significant change after only one week's therapy. Eosinophil recruitment to and activation in the area of antigen administration were already maximally reduced after 7 days, namely a reduction of 54, 52 and 59% at 10 h, and of 55, 68 and 66% at 24 h, respectively, at 7, 30 and 90 days. The area of induration was significantly reduced after one week of therapy. There was a general tendency towards an increase in the reduction at 30 and 90 days, which reached significance only at the 24 h observation; there was a 24, 51 and 48% reduction from baseline at, respectively, 7, 30 and 90 days. The data clearly show a progressive reduction of induration as well as of cellular events over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of glycopyrrolate on capsaicin-induced cough in normal volunteers treated with captopril.

The effects of inhibition of angiotensin converting enzyme (ACE) and glycopyrrolate on cough caused by inhaled capsaicin were investigated in a double-blind, randomised cross-over study in twelve normal volunteers. The capsaicin challenge was performed before and 2 h after dosing with 75 mg captopril or matched placebo given orally, and 20, 40 and 60 min after giving 1 mg glycopyrrolate i.v. to each subject. Captopril and placebo did not alter the cough response when compared to baseline. Glycopyrrolate, however, caused a significant increase in the threshold sensitivity (D2) from baseline, and a significant decrease in the total cough response at 40 and 60 min both after captopril and placebo. The D2-baseline and D2-40 min after glycopyrrolate (mean SD), respectively, were 3.2 (1.0); 17.9 (4.2) after placebo and 2.5 (8.5); 23.6 (6.9) after captopril. Elimination of vagal influences implies attenuation of the effects of tachykinins but not those prostaglandins. We postulate that tachykinins, such as substance P, play a more important role than prostaglandins in capsaicin-induced cough. We conclude that the vagus is important in the capsaicin-induced cough reflex, but, as suppression of this reflex by glycopyrrolate was delayed, the relevant receptors are either poorly accessible peripheral receptors or they are located in the central nervous system.