Common Cold - an Umbrella Term for Acute Infections of Nose, Throat, Larynx and Bronchi.

Acute respiratory tract infections, i. e. rhinitis, sinusitis, pharyngitis, laryngitis, bronchitis, belong to the most common medical conditions with a high economic burden. Nonetheless, there is little agreement concerning their differential diagnosis.This paper will discuss to what extent different anatomical sites of acute respiratory tract infections can be uniquely identified or whether the overlap and consecutive development in signs and symptoms renders these distinctions meaningless.Acute respiratory tract infections are variable but definition of diagnostic categories based on the anatomical sites of the dominant complaints shows that signs and symptoms both overlap to a great extent and/or emerge successively. Thus, in common cold distinguishing between acute symptom-based diagnoses arising from different anatomical sites of the aerodigestive system remains elusive. Therefore, preferred symptomatic treatments should foster a resolution of all possible symptoms as opposed to an isolated treatment of a single symptom (e. g. mucus hypersecretion) according to the presumed anatomical site (i. e. acute bronchitis).

Efficacy and tolerability of EPs 7630 tablets in patients with acute bronchitis: a randomised, double-blind, placebo-controlled dose-finding study with a herbal drug preparation from Pelargonium sidoides.

OBJECTIVE: Acute bronchitis is one of the most frequent health complaints for which patients seek medical advice. Although viral infections prevail, antibiotics are commonly prescribed. In this study, the efficacy and tolerability of EPs 7630 tablets, a herbal drug preparation from the roots of Pelargonium sidoides, were investigated in adults with acute bronchitis outside the strict indication for antibiotics. RESEARCH DESIGN AND METHODS: In this randomised, double-blind, placebo-controlled, multicentre dose-finding trial using an adaptive group-sequential design, 406 patients were randomly assigned to one of four parallel treatment groups (10 mg EPs 7630 tablets three times a day (30-mg group), 20 mg EPs 7630 tablets three times a day (60-mg group), 30 mg EPs 7630 tablets three times a day (90-mg group) or placebo three times a day) for a treatment period of 7 days. Primary endpoint was the change in the total score of bronchitis-specific symptoms (BSS) from baseline to day 7. RESULTS: Between day 0 and day 7, the mean BSS score decreased by 2.7 +/- 2.3 (placebo), 4.3 +/- 1.9 (30-mg group), 6.1 +/- 2.1 (60-mg group), and 6.3 +/- 2.0 points (90-mg group), respectively. The differences between the EPs 7630 groups and placebo were statistically significant (p < 0.0001, each). The secondary endpoints showed comparable results. EPs 7630 was well-tolerated. All documented adverse events were of mild to moderate intensity; their frequency was dose-dependent. No serious adverse events were reported. CONCLUSION: This study demonstrated statistically significant and clinically relevant superiority of all three tested dosages of EPs 7630 over placebo. All dosages of EPs 7630 were well-tolerated. Taking into account both efficacy and safety, the results of this study indicate that the 20 mg tablets of EPs 7630 taken three times daily constitute the optimal dose with respect to the benefit-risk ratio.

Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis - a randomized, double-blind, placebo-controlled multicenter trial with a herbal drug preparation from Pelargonium sidoides roots.

OBJECTIVE: The study aim was to demonstrate the efficacy and to investigate the tolerability of EPs 7630, a herbal drug preparation from Pelargonium sidoides roots, in the treatment of patients (1 - 18 years) with acute bronchitis outside the strict indication for antibiotics. MATERIALS AND METHODS: A total of 200 patients were randomized to receive either active drug containing EPs 7630 (1 - 6 years: 3 x 10 drops/d; > 6 - 12 years: 3 x 20 drops/d; > 12 - 18 years: 3 x 30 drops/d) or placebo for 7 consecutive days. PRIMARY OUTCOME MEASURE: change in the total score of bronchitis-specific symptoms (BSS) from Day 0 to Day 7. Main secondary outcome measures: treatment outcome, patients' satisfaction with treatment, onset of effect, bed rest. RESULTS: From baseline to Day 7, the mean BSS score improved significantly more for EPs 7630 compared with placebo (3.4 +/- 1.8 vs. 1.2 +/- 1.8 points, p < 0.0001). On Day 7, treatment outcome was significantly better (p < 0.0001), satisfaction with treatment more pronounced (77.6% vs. 25.8%, p < 0.0001), onset of effect faster, and time of bed rest shorter as compared with placebo. Tolerability was similarly good in both groups. All adverse events were assessed as non-serious. CONCLUSION: EPs 7630 was shown to be efficacious and safe in the treatment of acute bronchitis in children and adolescents outside the strict indication for antibiotics with patients treated with EPs 7630 perceiving a more favorable course of the disease and a good tolerability as compared with placebo.

Efficacy and tolerability of EPs 7630 in patients (aged 6-18 years old) with acute bronchitis.

AIM: For EPs-7630, a herbal drug preparation from Pelargonium sidoides roots, therapeutic effects in respiratory tract infections outside the strict indication for antibiotics have already been demonstrated in adults. Now, a dose-finding study for EPs-7630 was performed in children and adolescents. METHODS: A total of 400 patients (aged 6-18 years) were randomized to receive either 30 mg, 60 mg or 90 mg EPs-7630 or placebo daily. Primary outcome criterion was the change in the Bronchitis Severity Score (BSS) from day 0 to day 7. RESULTS: After 7 days of treatment, the change in the BSS total score was significantly better in the 60 mg and 90 mg groups compared with placebo that of the without relevant differences between these two dosages. Especially 'coughing', 'sputum' and 'rales at auscultation' improved under EPs-7630. Onset of effect was faster, time of bed rest shorter and treatment outcome and satisfaction with treatment were rated better. Tolerability was comparable with placebo in all treatment groups. CONCLUSION: EPs-7630 is effective in acute bronchitis outside the strict indication for antibiotics in 6-18 years old patients, with a dose of 60 mg or 90 mg daily offering the best benefit/risk ratio. EPs-7630 significantly reduces the severity of symptoms, leads to a more favourable course of the disease and a faster recovery from acute bronchitis compared with the placebo, and is well tolerated.

Formaldehyde inhalation & open field behaviour in rats.

BACKGROUND & OBJECTIVES: It has been shown in animal studies that repeated exposure to formaldehyde vapour alters behaviour and memory. Since information is not available on the behavioural consequences of acute formaldehyde exposure, this study was conducted to investigate the influence of single inhalative exposure to formaldehyde on the explorative and locomotor behaviour of adult male and female rats. METHODS: Rats were exposed to different concentrations of formaldehyde vapour (0.5, 1.0, 2.5%, corresponding to inhalation chamber concentrations of 1.0, 2.5, and 5.0 ppm, respectively) for 2 h and an open field test was carried out 2 h after the end of exposure (first test) and repeated 24 h thereafter (second test). The parameters examined were crossing of floor squares, sniffing, grooming, rearing, climbing, and defaecation. RESULTS: In exposed male rats, significant reduction of crossed floor squares, grooming, and wall climbing, and increase in floor sniffing and rearing were observed in the first test. During the second test, males in the groups exposed to 2.5 ppm and 5 ppm crossed significantly higher numbers of squares when compared to controls. Air sniffing, wall climbing, and rearing were altered in all exposed males. Control males showed higher incidence of defaecation in comparison to the values of first test. The formaldehyde-exposed female rats crossed significantly decreased numbers of floor squares in the first test. In females in the 2.5 ppm and 5 ppm groups, decreased grooming and enhanced floor sniffing were observed. In the second test, all exposed females crossed higher numbers of floor squares than controls. Frequencies of air and floor sniffing were higher in females exposed to 2.5 ppm and lower in those exposed to 1 ppm. Defaecation was enhanced in females in the 2.5 ppm group in comparison to the first test. INTERPRETATION & CONCLUSION: The results show that formaldehyde inhalation in the concentrations and duration of exposure used in the present experiments significantly influences the locomotor and explorative behaviour of rats after a single exposure in a gender-related manner and that various behavioural components in the exposed animals remains altered even after 24 h.

Sex-related differences in procarbazine-induced cleft palate and microgenia and the anti-teratogenic effect of prenatal folic acid supplementation in rats.

Sex-related differences in the frequency of cleft palates and microgenia in rat fetuses prenatally treated with procarbazine (200 mg/kg on day 14 of gestation (GD14), group 1), and the anti-teratogenic effect of prenatal folic acid supplementation (4 mg/kg on GD14 through GD17, group 2) were studied in LEW.1A rats. In group 1, complete clefts were observed in 69% of the male and in 36% of the female fetuses while incomplete clefts (present only in the hard palate) were exhibited by 31% of the males and 43% of the females. Microgenia occurred in all males but only in 64% of the female fetuses. In group 2, the prenatal folic acid supplementation significantly reduced the occurrence frequency of complete clefts to 9% in males and to 0% in females. In contrast, incomplete clefts increased to 82% in males and 91% in females. Microgenias were reduced to 73% and 57% in male and female fetuses, respectively. Since incomplete clefts present in the hard palate are assumed to be residues of spontaneous intra-uterine repair processes of exogenously induced complete palatal clefts, we conclude that prenatal supplementation with folic acid at a dose of 4 mg/kg promotes the intra-uterine repair of cleft palates and offers a partial protection against procarbazine teratogenicity. Furthermore, it is deduced that gender-specific differences exist in the susceptibility to procarbazine and in the anti-teratogenic effect of folic acid on procarbazine-induced microgenia.

A study on the effect of inhalative formaldehyde exposure on water labyrinth test performance in rats.

We investigated the effects of repeated inhalative exposure to several formaldehyde concentrations (2 hours/day, 10 consecutive days) on the behavior of adult male and female LEW.1K rats during a period in which they learned to perform a water labyrinth task. We also examined the effects on the histology of some organ tissues. While the controls needed increasingly shorter swimming periods to complete the water labyrinth test and made fewer errors with advancing trial duration, such progress could not be observed in the learning behavior of the exposed animals. They took significantly longer swimming periods to reach the finish and made significantly more errors in comparison to the controls. The statistical comparison between the collected data in the formaldehyde exposed male and female rats reveals that females in general reached the end point of the swimming labyrinth in significantly less time. On some trial days, however, they made more mistakes than males. In the highest concentration group, no gender differences were evident in the frequency of errors. The histological examination revealed no pathological changes attributable to formaldehyde exposure. Since the water labyrinth test is used to investigate changes in memory and learning behavior in animals, we conclude that under investigational conditions, formaldehyde affects the learning behavior and the memory of male and female rats.

Effects of prenatal procarbazine administration on intrauterine development in rats.

The effects of prenatal procarbazine (PCZ) administration on the intrauterine development of rat fetuses were investigated. Gravid rats were treated on day 14 of gestation (GD14) with 25 mg or 50 mg/kg body weight PCZ via stomach tube. Controls received normal saline in the same dosis and manner. On GD20, all fetuses were collected by caesarian section. Live and dead fetuses as well as resorptions were counted. In the live fetuses, the following investigations were conducted: measurement of body weight, occipito-coccygeal-lenght (OCL), tail length (TL), placental weight and diameter, external macroscopic and binocular microscopic examination, and sectional analysis of the animals using the razorblade sectioning technique. Both PCZ doses caused a significant reduction in the number of live fetuses and a significant increase in resorptions. Mean body weight in PCZ groups was antidromic affected. OCL and TL were significantly depressed. Placental weight and diameter as well as number of dead fetuses were comparable to those of controls. External and sectional investigations revealed no PCZ-related deviations. In the light of our findings we conclude that PCZ in the doses used in this experimental study significantly affects the intrauterine development in rats in terms of fetal toxicity but displays no teratological properties.

Is it possible to prevent cleft palate by prenatal administration of folic acid? An experimental study.

OBJECTIVE: In this study, folic acid was tested for its antiteratogenic effects on experimentally induced cleft palate in animals. DESIGN: Eleven pregnant Lew 1 A dams (75 fetuses) received 200 mg/kg procarbazine via gastric tubing on postconception (p.c.) day 14 to induce a cleft palate (CP); seven of the pregnant dams (45 fetuses) were additionally given 4 mg/kg folic acid subcutaneously from the 14th to the 17th day p.c. As a control group, three more pregnant dams (24 fetuses) were not treated with the drugs mentioned above. All fetuses were delivered by Caesarian section on day 20 p.c. OUTCOMES MEASURED: All fetuses were weighed and examined macroscopically with a stereomicroscope. Each fetal head was cut into 35 frontal sections and scrutinized histologically. RESULTS: None of the control fetuses (n = 24) exhibited a cleft. Without folate administration, 90% of the fetuses (27 of 30) that received procarbazine exhibited a CP. After additional prenatal folate administration, this rate remained virtually unchanged (91%; 41 of 45). However, the proportion of complete (total) CP (4%) was significantly (p <.0001) lower than in the group without folate (53%). Cleft-associated microgenia and microglossia were also significantly less frequent when folate was administered prenatally: microgenia was reduced by 22% (p =.029) and microglossia by 24% (p =.032). CONCLUSIONS: On the basis of these results, folate has a partial ameliorating effect on the teratogenicity of procarbazine given to pregnant rats. Additional studies are necessary on the effect of folate in different species, also taking cleft lip and CP into consideration.

Cheilognathopalatoschisis and its prophylaxis in animal experiments.

Cheilognathopalatoschisis (cleft lip, -maxilla, and -palate) is the second most frequent malformation in humans. The ontogenetic causes are mostly multifactorial. Some researchers have succeeded in lowering the frequency of occurrence of such clefts in children of predisposed women by giving the latter an applied symptomatic replacement therapy with multivitamin preparations or other substance classes during early pregnancy. However, the dosage of these substances was only anecdotal and their effect unspecific. Many research groups world-wide are conducting animal experiments in order to investigate the efficacy of vitamins and other substances as prophylactics. The experiments are usually conducted with laboratory rats and mice, and clefts are often induced by applying chemical noxa. The results of these trials, however, are controversial. Where some authors were able to prove protective effects of the vitamins or other substances they employed, others found evidence that such replacement therapy has no prophylactic effect. This paper provides insight into such studies with experimental animals, and compares their results.

Application of thiamine in preventing malformations, specifically cleft alveolus and palate, during the intrauterine development of rats.

OBJECTIVE: Animal experiments were conducted to test the reproducibility of previously documented antiteratogenic effects of thiamine on cleft formation in the craniofacial system. DESIGN: Thirteen gravid Wistar rats carrying 98 fetuses were given the hydrazine derivative procarbacine (200 mg/kg BW) on the fourteenth day postconception (PC) to induce malformations, chiefly cleft alveolus and palate (day of determining presence of sperm was called the first day PC). Seven of the treated gravid rats carrying 48 fetuses were additionally given a daily dose of 200 mg/kg thiamine from the thirteenth to the nineteenth day PC. OUTCOME MEASURES: A comparative analysis of the fetuses in both experimental groups was conducted externally and, for the skeleton, macroscopically using special staining techniques; the heads were analyzed using successional histologic sections; bodies were examined stereomicroscopically using the razor-blade sectioning technique. RESULTS: In 12 of the 16 parameters evaluated, no statistically significant differences were found between experimental groups. In some cases, we even observed an amplifying effect of thiamine on the development of malformations in the rat strain used in our study. CONCLUSIONS: Because several previous authors have repeatedly described treatment with thiamine as one of the sufficient prophylactic measures in slowing the development of viscerocranial malformations, especially cleft alveolus and palate, it is of utmost importance that the timing of treatment and dosage of thiamine be taken into consideration not only in animal experiments but also when applying results to humans.