Comparison of wheat and rye flour solutions for skin prick testing: a multi-centre study (Stad 1).

BACKGROUND: Skin prick testing (SPT) is the basic method for diagnosing IgE-mediated allergies. However, skin reactivity is related to the quality of allergen extracts, which are often poorly defined for occupational allergens. OBJECTIVE: To compare wheat and rye flour SPT solutions from different producers. MATERIALS AND METHODS: Standardized SPTs were performed in seven allergy centres with wheat and rye flour solutions from four producers in 125 symptomatic bakers. Optimal cut-off levels for weal sizes were assessed with the Youden Index. Comparisons between SPT results of different solutions were made with flour-specific IgE (sIgE) as the gold standard. Sensitivities, specificities, positive and negative predictive values, and test efficiencies were calculated and compared with McNemar and chi(2)-tests. The influence of the choice of the gold standard (sIgE or challenge) test was examined for 95 subjects. Additionally, SPT solutions were analysed for protein and antigen content. RESULTS: The optimal cut-off level for all SPT solutions was a weal size of >or=1.5 mm. While differences between wheat and rye flours were small, differences between producers were important. Variability of sensitivities (0.31-0.96), negative predictive values (0.42-0.91), and test efficiencies (0.54-0.90) were higher than variations of specificities (0.74-1.00) and positive predictive values (0.88-1.00). Similar results were obtained when using challenge test results as the gold standard. Variability could be explained by the different antigen contents of the SPT solutions. CONCLUSION: There is a wide variability of SPT solutions for wheat and rye flour from different producers, mainly with respect to sensitivities, negative predictive values, and test efficiencies. Improvement and standardization of SPT solutions used for the diagnosis of baker's asthma are highly recommended.

Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers.

BACKGROUND: Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours. AIMS OF THE STUDY: To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. METHODS: Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. RESULTS: Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. CONCLUSION: High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.

Computed tomographic high-attenuation mediastinal lymph nodes after aluminum exposition.

A case with increased computed tomographic densities of mediastinal lymph nodes with histologically proven aluminum storage is presented. We suggest consideration of aluminosis as differential diagnosis in patients with increased native CT densities beyond 50 HU.

Decreasing diffusion limitation on exercise in lower-graded interstitial lung disease.

In this study we investigated the contribution of diffusion limitation to the exercise-induced hypoxaemia in interstitial lung disease (ILD). We applied isotopic analysis to the composition of the stable isotopic oxygen molecules 16O2 and 16O18O in expiratory gas mixtures obtained from six ILD patients and six healthy subjects at rest and during ergometer work (60 W). The changes in the 16O18O/16O2 ratios were interpreted by using the overall fractionation factor of respiration (alpha O) which would be increased towards 1.03 on increasing diffusion limitation. In addition, the O2 partial pressures of alveolar gas and arterial blood (PAO2, PaO2) were determined. In the patients, alpha O was significantly reduced from 1.0066 +/- 0.0004 (mean +/- SD) at rest to 1.0035 +/- 0.0004 during exercise and in the healthy subjects from 1.0072 +/- 0.0008 to 1.0044 +/- 0.0004. Furthermore, the exercise-induced reduction of PaO2 (from 77 to 69 mmHg) was due to a drop of alveolar PO2 found in each patient, whereas in each healthy subject PaO2 was increased on exercise. On the basis of a resistance model we conclude that the patients' data were inconsistent with increasing diffusion limitation but showed an increasing impairment of O2 transport by ventilation.

Effects of low-dose epinephrine infusion on cardiovascular and renal responses to water immersion in humans.

Elevated plasma epinephrine concentrations may impair blood pressure homeostasis and renal sodium and volume excretion in response to central hypervolemia. We studied the effects of a low-dose epinephrine infusion (12 ng/kg/min) on cardiovascular and renal responses to a thermoneutral head-out water immersion in eleven healthy men. Responses to water immersion without epinephrine were characterized by significant suppression of plasma renin activity (PRA), plasma aldosterone concentration, and renal norepinephrine excretion, and an augmentation of natriuresis and diuresis. Epinephrine infusion, which raised mean plasma epinephrine concentration 4.3-fold, slightly increased plasma norepinephrine and renal norepinephrine excretion, markedly stimulated PRA (+66.7%), but decreased plasma aldosterone (-11.7%), and augmented renal sodium and volume excretion. Despite the presence of the epinephrine infusion, water immersion continued both to suppress PRA and aldosterone, and to increase natriuresis and diuresis in a qualitatively similar pattern. During all conditions blood pressure and heart rate remained unchanged. It is concluded that physiologic responses to central hypervolemia are not impaired at stress levels of circulating epinephrine. During epinephrine infusion, despite a concomitant increase in plasma norepinephrine and a stimulation of PRA, blood pressure remained constant in response to water immersion due to an augmentation of natriuresis and diuresis.

ACE inhibitor-induced cough and bronchospasm. Incidence, mechanisms and management.

A dry, tickly and often bothersome cough is the most common adverse effect of ACE inhibitors. Recent studies indicate that cough may develop in around 10% of the patients treated with ACE inhibitors. In half of these patients, the ACE inhibitor has to be discontinued. Cough has emerged as a class effect occurring with all ACE inhibitors with no clear difference between the single substances. While ACE inhibition is safe in the vast majority of patients with obstructive airways disease, asthmatic symptoms or exacerbation of asthma as well as a rise in bronchial reactivity have been occasionally reported. ACE inhibition increases the cough reflex. The mechanisms underlying ACE inhibitor-induced cough are probably linked to suppression of kininase II activity, which may be followed by an accumulation of kinins, substance P and prostaglandins. Physicians should be aware that a dry cough is the most common adverse effect of ACE inhibitors and that this symptom may occur not necessarily shortly after institution of therapy but months or even a year later. Replacement by another ACE inhibitor should not be tried, since the cough will almost always recur on rechallenge with the same or another ACE inhibitor. After withdrawal of the ACE inhibitor, which is the treatment of choice, cough will resolve usually within a few days.

Effects of sympathetic inhibition on blood pressure and renal responses to central hypervolaemia in normal humans.

The purpose of this study was to evaluate the effects of short-term sympathetic inhibition with clonidine on blood pressure and renal responses to central hypervolaemia induced by thermoneutral head-out water immersion. Eleven healthy subjects were randomly studied on two occasions, during a 1 h pre-immersion period, 2 h of water immersion and a 1 h post-immersion period, after either placebo or clonidine treatment. Clonidine caused a significant suppression of plasma adrenaline, plasma noradrenaline, urinary noradrenaline excretion and mean arterial blood pressure. Blood pressure remained constant during water immersion after both placebo and clonidine, compared with the respective pre-immersion control values. The suppression pattern of plasma catecholamines and urinary noradrenaline in response to water immersion during placebo was similar after clonidine treatment. Renal volume excretion was not affected by clonidine. In contrast, clonidine caused a significant attenuation of the immersion-induced stimulation of natriuresis (maximum -33 +/- 12%, P < 0.01, compared with placebo). These data indicate that the renal capacity to excrete sodium is impaired during moderate blood pressure reduction by short-term sympathetic inhibition with clonidine, whereas the regulation of arterial blood pressure in response to central hypervolaemia is maintained.

Role of epinephrine-induced hypokalemia in the regulation of renin and aldosterone in humans.

Circulating epinephrine induces both stimulation of plasma renin activity (PRA) and a decrease in serum potassium concentration. This study was designed to determine the dose-response effects of systemic epinephrine infusion on the relationship of PRA and plasma aldosterone concentration. Twenty-one men with normal blood pressure received either an intravenous infusion of epinephrine at 12.5, 25, and 50 ng/(kg x min) by stepwise increments for 1 hour each or isotonic saline solution. Infusion of epinephrine led to a dose-dependent increase in plasma epinephrine concentration, systolic blood pressure, and heart rate, whereas diastolic blood pressure was decreased. PRA was elevated in a dose-dependent manner, whereas the plasma aldosterone concentration was reduced. During infusion of epinephrine, the serum potassium concentration and renal potassium excretion were significantly decreased. We conclude that despite marked stimulation of PRA, the plasma aldosterone concentration was further decreased because of a dose-dependent decrease in serum potassium concentration induced by epinephrine. Thus hypokalemia appears to be the predominant regulator of plasma aldosterone during incremental epinephrine infusion.

Functional inhomogeneities in interstitial lung disease, assessed using (16)o(18)o.

Abstract We investigated the contribution of diffusion limitation and functional inhomogeneities to the impairment of pulmonary oxygen (O(2)) transfer in interstitial lung disease (ILD). Analyses of (16)O(18)O/(16)O(2) ratios were performed on expiratory gas mixtures obtained from 6 ILD patients and 6 healthy humans at rest, applying respiratory mass spectrometry. We assessed O(2) transport by using the overall fractionation factor of respiration (α(0)) which is predicted to increase in the case of diffusion limitation. α(0) was reduced in patients (1.0065±3.10(-4)) when compared to the value for healthy subjects (1.0071±7.10(-4), P <0.05), pointing away from a diffusion limitation of O(2) transport. On the basis of a two-compartment model we interpreted our findings by assuming an unequal distribution of diffusion and convective O(2) transport in the pulmonary gas exchange of the patients.

Age is a major determinant of the divergent blood pressure responses to varying salt intake in essential hypertension.

Blood pressure responses to 1 week of low (20 mmol sodium/day) and high (300 mmol sodium/day) salt intake were investigated in a double-blind, randomized study in 46 white, nonobese subjects with essential hypertension (13 women, 33 men; mean age 45.3 +/- 2.2 years, age range 25 to 80 years). The individuals were classified as salt-sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high salt intake, as salt-resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counter-regulators" when mean arterial blood pressure fell by at least 5 mm Hg during the high salt diet. Mean arterial blood pressure of all subjects taken together increased from 101.9 +/- 1.4 mm Hg during salt restriction to 103.7 +/- 1.5 mm Hg (P < .05) during salt loading. Eleven subjects (23.9%) were classified as salt-sensitive, 27 (58.7%) as salt-resistant, and 8 (17.4%) as counter-regulators. Multiple regression analysis revealed that age, but not baseline blood pressure, sex, body mass index, or family history of hypertension contributed significantly to the change in blood pressure following the diets. Ten of the 11 salt-sensitive subjects were older than the median age of 45 years. In salt-sensitive, as compared to salt-resistant, hypertensive subjects, creatinine clearance was lower and plasma renin activity was suppressed at baseline as well as during low and high salt intake. In contrast, plasma concentrations of norepinephrine and atrial natriuretic peptide were elevated in salt-sensitive subjects. These differences between the groups appeared, at least partially, to be age-related.(ABSTRACT TRUNCATED AT 250 WORDS)

[Potassium citrate versus potassium chloride in essential hypertension. Effects on hemodynamic, hormonal and metabolic parameters]. / Kaliumcitrat versus Kaliumchlorid bei essentieller Hypertonie. Wirkung auf hämodynamische, hormonelle und metabolische Parameter.

A study was conducted on 25 patients (18 men, seven women; mean age 48 [24-70] years) with essential hypertension (EH) to see whether an increase in potassium supply influences blood pressure as well as metabolic and hormonal parameters, and whether the anion administered together with potassium affects the results. In a randomized, cross-over trial sequence the patients daily received 120 mmol potassium chloride, 120 mmol potassium citrate or a placebo, each for 8 weeks. Between each of the three periods there was a "wash-out" phase of 4 weeks each. After 8 weeks of potassium citrate intake the systolic and diastolic pressures were reduced significantly, by a mean of 6.2/3.8 mm Hg (P < 0.05). But after potassium chloride there was only a small, not significant, reduction. Metabolic and hormonal parameters (fasting glucose concentration, glucose tolerance test, lipid electrophoresis; plasma renin activity, plasma concentration of aldosterone, noradrenaline and insulin) were not significantly changed.--These findings suggest that an increased supply of potassium has a favourable haemodynamic effect, but this varies markedly between different potassium salts. An increase in potassium supply should thus be considered as an additional measure in the treatment of EH. As long as renal function is normal no unfavourable metabolic effect need be feared.

[Primary amyloidosis of the lung]. / Primäre Amyloidose der Lunge.

We report on a female patient of 66 years of age in whom primary nodular amyloidosis of the lung was diagnosed on the basis of a chance radiological finding. Based on this case report we discuss the pathophysiology, diagnosis and clinical findings of pulmonary amyloidosis.

Dissociation of renin and aldosterone during low-dose epinephrine infusion.

Besides its dose-dependent alpha- and beta-adrenoceptor-mediated vascular action, hormonal effects of epinephrine also involve the activation of renin secretion by direct stimulation of renal beta 1-adrenoceptors. To determine the interrelation between increased plasma renin activity in response to epinephrine and plasma aldosterone concentration and renal excretion of potassium and sodium, 26 normal subjects were subjected to 4 h of an intravenous infusion of low-dose epinephrine (12 ng/kg/min). Epinephrine infusion raised mean plasma epinephrine concentration 2.8-fold above control (P < .001). Plasma renin activity (PRA) increased by 56% (P < .01) during epinephrine infusion, whereas plasma aldosterone concentration remained constant. Infusion of epinephrine also resulted in markedly suppressed urinary potassium excretion (-32%; P < .025), while urinary sodium excretion was not altered. Serum potassium was decreased by 4.1% during epinephrine (P < .025). Systolic blood pressure and heart rate did not change, and diastolic blood pressure was slightly reduced by 5 mm Hg (P < .025). In summary, during low-dose epinephrine infusion PRA is markedly increased while plasma aldosterone remains unchanged. The fall in urinary potassium excretion in the presence of reduced serum potassium concentration is most likely mediated via the beta-adrenoceptor-mediated shift of potassium into cells. This in turn may prevent a concomitant rise of plasma aldosterone, which subsequently contributes to the blunted kaliuresis and unchanged natriuresis found during the epinephrine-induced rise of PRA. In conclusion, the epinephrine-induced fall in serum potassium appears to be the predominant regulator of plasma aldosterone concentration even in the presence of a stimulated PRA.

ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.

PURPOSE: Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated. PATIENTS AND METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks. RESULTS: Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection). CONCLUSION: This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.

Perindopril plus nifedipine versus perindopril plus hydrochlorothiazide in mild to severe hypertension: a double-blind multicentre study. The Multicentre Study Group on Treatment Association with Perindopril.

Thiazide diuretics are considered as the choice drug to combine with ACE inhibitors for the treatment of hypertension. However, there is much evidence showing that the combination of ACE inhibitors with a calcium channel blocker is effective and safe. We compared the safety and efficacy of perindopril 8 mg once daily plus nifedipine SR 10 mg twice daily with perindopril 8 mg once daily plus hydrochlorothiazide (HCTZ) 12.5 mg once daily in a two phase three month study. After a one month placebo run-in period, patients whose DBP averaged 95-125 mmHg received perindopril 4 mg once daily for the first open phase (n = 524). After one month those whose DBP remained > 90 mmHg were prescribed perindopril 8 mg once daily for a second month. Among them, those whose DBP were still > 90 mmHg entered the second phase for one month, in a double-blind fashion. Fifty-three patients received HCTZ (BP: 161.2/99.2 +/- 2.0/0.9 mmHg), 57 received nifedipine (BP: 161.4/98.7 +/- 2.2/0.7 mmHg). Five patients withdrew due to side-effects, three patients in the perindopril plus nifedipine group and two in the perindopril plus HCTZ group. After one month there was a significant drop in BP (P < 0.01) in both groups: perindopril plus HCTZ (-13.9/-11.9 mmHg) and perindopril plus nifedipine (-12.1/-10.8 mmHg). Heart rate was not significantly modified: perindopril plus HCTZ (-1.30 beats/min), perindopril plus nifedipine (+0.54 beats/min). There were no significant difference between the two combinations for BP reduction and heart rate. The incidence of adverse experiences was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of severe and moderate salt restriction on serum lipids in nonobese normotensive adults.

The effects of severe and moderate sodium restriction on blood pressure and serum lipids were studied in nonobese normotensive adults. Subjects (n = 163) were given a low (20 mmol Na/d) and high (300 mmol Na/d) salt diet for 1 week each in random order. Of these subjects, 25 were selected to participate in a second study with moderate salt restriction (85 mmol na/d) or "normal" sodium diet (200 mmol Na/d) given for 4 weeks each in random order. After severe salt restriction, 19% of the 163 subjects had a significant decrease in blood pressure (salt-sensitive), 15% showed a significant rise (counter-regulator), and 66% exhibited no change (salt-resistant). Severe sodium restriction increased serum total and low density lipoprotein (LDL) cholesterol and triglycerides. After correction for hematocrit, the changes in blood lipids remained significant in the counter regulators only. After moderate salt restriction, serum lipid concentrations and blood pressure did not change.

Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects.

Blood pressure responses to 1 week of low-salt (20 mmol sodium/d) and high-salt (300 mmol sodium/d) intake were investigated in a single-blind randomized study in 163 white, nonobese normotensive subjects (65 women and 98 men; mean age, 38 +/- 1.2 years). The individuals were classified as salt sensitive when mean arterial blood pressure rose by at least 5 mm Hg during high-salt intake, as salt resistant when mean arterial blood pressure changed by less than 5 mm Hg, and as "counterregulator" when mean arterial blood pressure fell by at least 5 mm Hg during the high-salt diet. Reexamination of 31 subjects showed that this approach to the testing of salt sensitivity was reliable and reproducible. Thirty subjects (18.4%) were classified as salt sensitive, 108 (66.3%) as salt resistant, and 25 (15.3%) as counterregulators. Multiple regression analysis revealed that age, body weight, and family history of hypertension contributed significantly to the change in blood pressure after the diets. Salt sensitivity was more frequent in older subjects and in those with a positive family history of hypertension. An increase in blood pressure after salt restriction was more likely in younger individuals and in those with a negative family history of hypertension. Plasma renin activity and plasma aldosterone concentrations were lower in salt-sensitive compared with salt-resistant and counterregulating subjects. The rise in plasma renin activity during salt restriction was most pronounced in counterregulating subjects. Plasma norepinephrine concentrations were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurohormonal and metabolic effects of severe and moderate salt restriction in non-obese normotensive adults.

OBJECTIVE: The effects of severe and moderate sodium restriction on blood pressure, neurohormonal activity and serum lipids were studied in non-obese normotensive adults. METHODS: In the first part of the study, 163 subjects were randomly assigned to a diet of 20 or 300 mmol/day sodium for 1 week each. In the second part, 25 subjects were given a diet of 85 or 200 mmol/day sodium for 4 weeks each in random order. RESULTS: After severe salt restriction 19% of the subjects had a significant decline (salt-sensitive group), 15% showed a significant rise (counter-regulator group) and 66% exhibited no change in blood pressure (salt-resistant group). Severe sodium restriction increased plasma renin activity and noradrenaline concentration, as well as serum total and low-density lipoprotein-cholesterol and triglycerides. After correction for haematocrit, only the changes in total and low-density lipoprotein-cholesterol remained significant. The rise in plasma renin activity during salt restriction was steeper in the counter-regulator group than in the other groups, whereas the changes in plasma noradrenaline concentrations were similar in all groups. During moderate salt restriction, plasma renin activity and noradrenaline concentration were significantly increased, but serum lipid concentrations and blood pressure did not change. CONCLUSION: In non-obese normotensive adults, severe and moderate salt restriction stimulates neurohormonal activity. In contrast to severe salt restriction, a moderate reduction in dietary salt intake does not influence blood lipids in normotensive subjects.