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Background and Aim: Pemphigoid gestationis (PG) is a rare skin disease of pregnancy. Given its incidence in pregnant women, physicians and especially obstetricians may not encounter this diagnosis in their entire career. We find this to be a major problem and there is an obligation to report it in as much detail as possible along with recommended treatments with proven efficacy., Case Report: We describe the case of a 27 year old patient who was referred to the dermatology department with severe dissemination of blisters in the 9th week of pregnancy. She was diagnosed with pemphigoid gestationis in her first pregnancy. High doses of corticosteroids were initiated but due to inadequate effect cyclosporine was added. The pregnancy was complicated with gestational diabetes. The patient gave birth in her 33rd week by caesarian section due to premature rupture of the membrane. Vesicles were seen on the newborn immediately after birth which diminished spontaneously over 2 weeks. Blisters were still seen on the patient 1 month after labor even with the combination of systemic corticosteroids with cyclosporine., Conclusion: PG is a rare dermatosis of pregnancy. The course of the disease can be severe, necessitating systemic therapy. As described in this patient, systemic corticosteroids may not be sufficient and adding another immunosuppressive treatment may be needed. If pemphigoid gestationis has occurred during a previous pregnancy it is advised to reconsider another pregnancy., Competing Interests: The authors report no conflicts of interest in this work.

Objectives: This study evaluated complications that can occur during planned home births that require transfer to the hospital. These factors were assessed to improve the current status of deliveries performed outside health care facilities in the Czech Republic., Materials and Methods: This prospective cohort study included data on 105 cases of complicated home births during 2017 to 2021 using an online form accessible to all hospital maternity wards in the Czech Republic., Results: Planned home births were complicated by fetal/neonatal causes, maternal causes, and combined fetomaternal complications in 28 (26.7%), 20 (19%), and 2 (1.9%) cases, respectively. The need for transfer was most often realized after the birth of the fetus (86; 81.9%); however, it was realized during birth in 19 (18.1%) cases. The following complications were noted most often: postpartum hemorrhage (23; 21.9%); neonatal asphyxia (17; 16.2); placental retention (14; 13.3%); birth injury (12; 11.4%); neonatal hypothermia (5; 4.8%); and placental birth (5; 4.8%). Indications for transfer during labor were as follows: labor obstruction (10; 9.5%); fetal hypoxia (5; 4.8%); bleeding during labor (2; 1.9%); preeclampsia (1; 0.9%); and fetal malformation (1; 0.9%). Perinatal death occurred in 8 (7.6%) cases. Permanent neonatal morbidity occurred in 4 (3.8%) cases., Conclusions: Patients with home birth complications were transferred to the hospital most often after the birth of the fetus. The low proportion of transfers during childbirth is caused by the unprofessional management of planned home births, resulting in a high number of perinatal deaths and high rate of permanent neonatal morbidity.

Objectives: Postpartum retained products of conception are a relatively rare diagnosis occurring in approximately 1% of cases after spontaneous deliveries and abortions. The most common clinical signs are bleeding and abdominal pain. The diagnosis is based on clinical signs and ultrasound examination., Material and Methods: Retrospective analysis of 200 surgical procedures for the diagnosis of residua postpartum obtained in 64 months. We correlated the method and accuracy of diagnosis with definitive histological findings., Results: During 64 months, we performed 23 412 deliveries. The frequency of procedures for diagnosis of retained products of conception (RPOC) was 0.85%. Most (73.5%) of the D&C were performed within six weeks of delivery. Histologically, the correct diagnosis was confirmed in 62% (chorion + amniotic envelope). There was interestingly lower concordance of histologically confirmed RPOC in post-CS patients (only 42%). In women after spontaneous delivery of the placenta, the diagnosis of RPOC was confirmed by histological correlate in 63%, and the highest concordance occurred in women after manual removal of the placenta in 75%., Conclusions: Concordance with histological findings of chorion or amnion was seen in 62% of cases; this means that the incidence rate in our study was around 0.53%. The lowest concordance is after CS deliveries, 42%. D&C for RPOC should be performed after adequate clinical evaluation and in the knowledge of 38% false positivity. There is certainly more space for a conservative approach under appropriate clinical conditions, especially in patients after CS.

Objectives: The good healing of the hysterotomy after cesarean section is important for subsequent pregnancies. However, the factors which improve this healing have not been completely described, yet. In this study, we focused on factors which may affect healing of hysterotomy within one year after delivery, such as menstruation, breastfeeding, and the use of the contraception., Material and Methods: Following delivery, total of 540 women were invited for three consecutive visits at six weeks, six months, and 12 months postpartum. The presence of menstruation, frequency of breastfeeding and contraception use were recorded. The scar was evaluated by vaginal ultrasound as already described. The impact of menstruation, breastfeeding, and contraception method on presence of niche was evaluated., Results: The presence of menstruation increased odds to have niche by 45% (CI 1.046-2.018, p = 0.026). Secondarily, our results demonstrated a statistically significant protective effect of breastfeeding on the incidence of niche with OR 0.703 (CI 0.517-0.955, p = 0.024). Breastfeeding decreases odds to have niche by 30%. Also, the use of gestagen contraception lowered the odds by 40% and intrauterine device (IUD) or combine oral contraceptive (COC) by 46.5%. The other possibly intervening factors were statistically controlled., Conclusions: Amenorrhea, breast-feeding and progesterone-contraceptive decreases the risk of uterine niche within one year follow up.

Background: Surgical treatment of obese female patients represents a real challenge. Over the last decade, minimally invasive techniques for hysterectomy have emerged. These approaches reduce the invasiveness of standard surgical procedures while maintaining efficacy and feasibility., Objective: To evaluate the rates of perioperative, early, mid-term and late postoperative complications in very obese [body mass index (BMI) ≥ 35 and < 40 kg/m 2 ] and severely obese (BMI ≥ 40 kg/m 2 ) women who underwent total (non-radical) hysterectomy., Design: A prospective comparative multi-centre non-randomized study., Methods: In total, 328 consecutive total (non-radical) hysterectomies were performed at seven teaching gynaecological centres. Of these, 153 (46.6%) were performed using an open laparotomy (LT) approach and 175 (53.4%) were performed laparoscopically (LS). All data were collected by medical specialists at the pre-operative examination prior to surgery, during surgery and three times postoperatively (during hospital stay, at 6-week follow-up and 6 months following surgery). Another analysis considered a total of 206 women who underwent laparoscopic hysterectomy. The subjects were divided according to BMI into 120 very obese women (BMI ≥ 35 and < 40 kg/m 2 ) and 86 severely obese women (BMI ≥ 40 kg/m 2 )., Results: The total number of composite perioperative complications was significantly lower in the LS group (p = 0.006). Composite complications occurred significantly more often in patients in the LT group compared with the LS group in the early (p < 0.001) and mid-term (p < 0.001) postoperative periods. In the late postoperative period, the total number of composite postoperative complications did not differ significantly between the groups (p < 0.396). Among 206 patients who underwent laparoscopic hysterectomy, the number of complications was generally low; the rates of composite perioperative (p = 0.393), early (p = 0.642), mid-term (p = 0.738) and late (p = 1) postoperative complications were generally low; and frequency did not differ significantly with BMI., Conclusion: The LS approach does not increase intra-operative morbidity associated with surgery, and has significantly better outcomes in terms of the postoperative complication rate., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To demonstrate the use of a single-stapler technique during rectosigmoid resection in women with deep infiltrating endometriosis (DIE)., Design: A step-by-step video demonstration of rectosigmoid resection and end-to-end anastomosis using two circularly placed sutures and one circular stapler., Setting: Institute for the Care of Mother and Child, Prague, Czech Republic., Patient(s): A 39-year-old woman presented with primary sterility and deep infiltrating endometriosis, and an EZIAN score of A2,B2,C3. A nodule was located 9 cm from the anus and was 38 × 9 mm in size. This included an intramural fibroma of 6 cm and a left-sided ovarian endometriotic cyst of 6 cm. Her pain on the visual analogue scale were dysmenorea 6, dyspareunia 5-6, dyschezie 7, dysuria 0, and acyclic pain 5., Interventions: The primary objective was to replace the linear-stapler resection with two simple, strictly circularly placed sutures, to cut the intestinal wall between them, and to form the end-to-end anastomosis with a circular stapler. The one-stapler technique consisted of the following steps: intestinal wall cleansing as in the limited segmental resection; placement of one strictly circular suture just below the DIE nodule, without fixation; placement of the first circular suture just below the DIE nodule, ideally with at least three full-thickness "bites" of the intestinal wall; placement of the second circular stitch approximately 2 cm below the first one in a similar manner (three full-thickness "bites"); interruption of the intestinal wall with a harmonic scalpel; end-to-end intestinal anastomosis with a circular stapler; and airtightness test of the anastomosis. This results in only one incision line and therefore a lower risk of leakage. Intestinal resection time was on average 10 minutes longer compared to that for the linear stapler technique. So far, we have successfully performed the procedure in 25 women. Perioperative leakage was observed in two of these 25 patients in the classical procedure group and in none of the 25 patients in the group with the one-stapler technique. There were no differences in C-reactive protein (CRP) on third and fifth postoperative days or in other complications such as bleeding and pyrexia). The cost of procedure is lowered by the decrease in the number of staplers from 3 to 1. The patients' postoperative follow-up was uneventful, and they were discharged from the hospital at the same time as the women in whom the classical stapler technique was performed., Main Outcome Measures(s): The primary outcome was the development of a new surgical approach to resection rectosigmoid endometriotic nodules that would decrease the number of incision lines on the intestine. The secondary outcome measures were peri- and postoperative complications (i.e., bleeding, intestinal leakage, postoperative infection, CRP), length of the surgery and hospitalization, and cost of the procedure., Conclusion: Multiple incision lines following resection of the rectosigmoid colon and end-to-end anastomosis are risk factors for postoperative intestinal leakage. Therefore, a single incision line formed with two circular sutures, and one circular stapler may reduce the risk of postoperative complications and also financial expenses of the procedure. We believe that this method is suitable and easiest for nodules located less than 6 cm from the anal verge because of possible complications with angulation of linear stapler., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: This study compared healing of the scars after cesarean section during the first postpartum year using a single- or double-layer suturing technique. Scarring was assessed by a transvaginal ultrasound. We explored the appearance and localization of uterine scars with regard to the obstetric history. Our aim was to compare the position of the scar or defect, if present, its dimensions, and any residual myometrium with respect to the suturing technique during the cesarean section., Material and Methods: Women with uncomplicated singleton pregnancies indicated for elective or acute cesarean section were randomly allocated to the uterine closure technique group. During the first postpartum year, their lower uterine segment was examined with a transvaginal ultrasound in three consecutive visits at 6 weeks, 6 months and 12 months., Results: 324 women attended the 12-month visit; of these, 149 underwent single-layer closure of the uterine incision and 175 double-layer technique. A higher proportion of the defects is seen in the single-layer closure technique of suturing. Defects in the single-layer group were wider (0.002) and the residual myometrial thickness in the single-layer group were thinner (0.019). Women who underwent cesarean section at the stage of full cervical dilation had scars that were closer to the external cervical os (0.000). The position of the uterus varies greatly between controls (0.000). The combination of uterine position and scar defect presence changed significantly between controls (0.001), and was significantly dependent on the suturing method (0.003). Defects with or without contact with the uterine cavity changed statistically between controls (0.017). Both types of defects were more common in the single-layer closure technique group., Conclusions: The findings of this study demonstrate that double-layer technique with the first continuous nonlocking suture followed by a second continuous nonlocking suture is associated with better suture healing and greater residual myometrial thickness. No difference was observed between single- and double-layer closure for the presence of maternal infectious morbidity, wound infection or blood transfusion., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction and Hypothesis: Endometriosis is a gynecological condition characterized by endometrial tissue outside of the uterus. It affects up to 15% of women of reproductive age. In the case of bowel infiltration, about 90% of lesions are localized on the sigmoid colon or the rectum and may interfere with bowel function. Three surgical approaches are possible: (1) shaving technique, (2) discoid resection of the nodule, and (3) segmental resection with end-to-end anastomosis. A rectovaginal fistula is feared as a postoperative complication mainly in simultaneous resection of the vaginal and the rectosigmoid nodules. Its prevention is a two-step surgery (the first operation on the vagina and the second on the colon) or a preventive colostomy, both of which are often thought to be too invasive for a benign condition. Herein, we suggest a one-step surgery to prevent its development., Methods: In three women, a concomitant laparoscopic resection of the vaginal and rectosigmoid endometrial nodule was completed with interposition of a mesorectal flap., Results: All surgeries were uncomplicated with no rectovaginal fistula in the postoperative period., Conclusion: In the hands of skilled surgeons, this one-step technique can be used to prevent rectovaginal fistula development.

Introduction and Hypothesis: First vaginal delivery severely interferes with pelvic floor anatomy and function. This study determines maternal and pregnancy-related risk factors for pelvic floor dysfunction (PFD), including urinary incontinence (UI), urgency, anal incontinence (AI), pelvic organ prolapse (POP) and levator ani muscle (LAM) avulsion., Methods: This is a single-centre prospective observational cohort study on healthy women in their first singleton pregnancy. All underwent clinical and 3D transperineal ultrasound examination at 6 weeks and 12 months postpartum. Objective outcomes were POP-Q and presence or absence of LAM trauma. Functional outcomes were measured by the ICIQ-SF and PISQ 12. Multivariate regression was performed to determine birth and maternal habitus-related risk factors for UI, urgency, AI, dyspareunia, LAM avulsion and ballooning., Results: Nine hundred eighty-seven women were included. Risk factors for UI were maternal age per year of age (OR: 1.09; 95% CI: 1.04-1.13; p = 0.0001) and BMI before pregnancy (OR: 1.08; 95% CI: 1.04-1.13; p = 0.001); for POP stage II+ maternal age (OR: 1.08; 95% CI: 1.08-1.14; p = 0.005). Avulsion was more likely after forceps (OR: 3.22; 95% CI:1.54-8.22; p = 0.015) but less likely after epidural analgesia (OR: 0.58; 95% CI: 0.37-0.90; p = 0.015) and grade I perineal rupture (OR: 0.50; 95% CI: 0.29-0.85; p = 0.012). Ballooning was more likely at increased maternal age (OR: 1.08; 95% CI: 1.02-1.13; p = 0.005), epidural (OR: 1.64; 95% CI: 1.06-2.55; p = 0.027) and grade I perineal rupture (OR: 1.79; 95% CI: 1.10-2.90; p = 0.018)., Conclusion: Though maternal characteristics at birth such as age or BMI increase the risk of PFD, labour and birth factors play a similarly important role. The most critical risk factor for MLA avulsion was forceps delivery, while an epidural had a protective effect.

Hyperoxia-induced lung injury is well known in animal and human studies. The respiratory epithelium including sensory nerve endings is a major target for oxidative injury that manifested in lung function changes including cough. On the basis of available information we supposed that hyperoxia alone or in combination with primary lung tissue injury should have a damaging effect on lungs, including the airway nerve endings with the changes in the sensitivity of the central and peripheral neuronal pathways regulating cough. We have previously demonstrated that long-term exposure to 100% oxygen inhibits the cough reflex in cat. This review article summarizes the effect of hyperoxia on the cough reflex in guinea pig model using different concentrations of oxygen and different time of exposure. We also present information on the potential role of antioxidants in reversal of the detrimental effects of hyperoxia on coughing and additional analysis of experiments from previously published studies were obtained and analysed for the cough reflex sensitivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the outcomes with the use of Dilapan-S for cervical preparation prior to medical or surgical abortion., Study Design: International, multicentre, prospective observational study in women between 6 + 0-24 + 0 weeks' gestation. The study was conducted across 7 study sites in 4 countries, between 1/5/2015 to 31/12/2016. The primary outcomes studied were the number of dilators used and the duration required for cervical preparation prior to abortion. Secondary outcomes were complications of dilator use and infection. Participants were followed-up for 4 weeks post procedure to capture any delayed complications., Results: A total of 483 women were enrolled with 439 women eligible for analysis. Medical abortion was performed in 38% (n = 165) women and surgical abortion in 62% (n = 274). For medical abortions and surgical abortions, an average of 3 osmotic dilators for time interval of 4-7 hours provided effective cervical preparation. Medical abortions were performed as day-case procedures (<12 h) in 81% of women. There was no difference in using either adjunctive misoprostol or Dilapan-S followed by misoprostol for cervical ripening effect to achieve complete medical abortion. Dilapan-S permitted surgical abortions to be performed as same-day procedures (<12 h), in 85% of women regardless of gestational age and without the need to use adjunctive or additional misoprostol. There were no serious adverse events reported with the use of Dilapan-S, including in women with a previous caesarean section. The overall infectious morbidity was 0.9% of cases with no causal relationship with the use of synthetic osmotic dilator use (for a length <24 h). In addition, Dilapan-S was reported as easy to insert and remove in over 90% of women., Conclusion: Dilapan-S is a safe and effective method for cervical preparation for medical and surgical abortions up to 24 weeks' gestation. It allows medical and surgical abortions to be performed as day case procedures and is associated with a low complication rate. Future research should aim at directly comparing Dilapan-S and preferred pharmacological agents in a randomised controlled trial., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: In the Czech Republic (CR), it is possible, to carry out Medical Termination of Pregnancy (MToP) in the 1st trimester since June 2014, in case a woman submits a written request for it and in case the ultrasound examination confirms an intrauterine singleton prosperous pregnancy, between day 42 and 49 of gestation, crown-rump length (CRL) of the embryo 2-9 mm. The aim of the study is to analyze the management of MToP up until the 7th week of gestation in five centres in the CR., Design: Multicenter cohort (prospective) study., Setting: Department of Obstetrics and Gynecology, Palacky University Olomouc, Faculty of Medicine and Dentistry, University Hospital Olomouc; The Institute for the Care of Mother and Child, Charles University in Prague, Third faculty of Medicine; Department of Gynecology and Obstetrics, Charles University in Prague, First faculty of Medicine, General University Hospital in Prague; Department of Gynecology and Obstetrics, Charles University in Prague, First faculty of Medicine, Hospital Na Bulovce, Prague; Department of Gynecology and Obstetrics, Masaryk University, Faculty of Medicine, University Hospital Brno., Methods: In 2014-2016, a total of 1820 pregnant women requested MToP. The diagnosis of an intrauterine singleton prosperous pregnancy was set by transvaginal ultrasound, CRL 2-9 mm. MToP was carried out by combination of mifepristone (600 mg orally) and misoprostol (400 mcg orally) within 48 hours. MToP follow up (exclusion of ongoing pregnancy) after 2-3 weeks was carried out by transvaginal ultrasound as well., Results: In 11.0% of women (201/1820) who requested MToP, CRL > 9 mm, unprosperous, multiple or ectopic pregnancy was diagnosed. In the remaining 1619 women MToP was carried out, but in 221 cases (13.7%) at least one additional pre-first visit was needed before the diagnosis of intrauterine singleton prosperous pregnancy CRL 2-9 mm could be established, in 19 cases (1.2%) two pre-first visits and in 5 cases (0.3%) even three. Gestational age was 42-49 days (average 47.1, median 47), the women were 14-47 years of age (average 30.7, median 30). In 20.8% of women (336/1619) MToP follow up was missed and of the remaining 1283 women, ongoing pregnancy (MToP failure) was diagnosed in 1.6% (24/1283), incomplete abortion in 6.5% (83/1283) and complete abortion in 91.9% (1179/1283). A subsequent surgical intervention was carried out in 7.1 % of women (91/1283)., Conclusion: A medical facility performing MToP in the 1st trimester should develop its own methodology in accordance with the legislation in force, Summaries of Product Characteristics, and recommendations of professional associations. The methodology should also include a method of evaluation of the result and management. The subsequent surgical intervention should only be performed in indicated cases. The main goal of MToP follow up is to exclude ongoing pregnancy (MToP failure), and the patient should be informed in detail about the risks involved and possibilities of their solution, it is necessary to obtain an informed consent.

The effect of volume-related feedback and output airflow resistance on the cough motor pattern was studied in 17 pentobarbital anesthetized spontaneously-breathing cats. Lung inflation during tracheobronchial cough was ventilator controlled and triggered by the diaphragm electromyographic (EMG) signal. Altered lung inflations during cough resulted in modified cough motor drive and temporal features of coughing. When tidal volume was delivered (via the ventilator) there was a significant increase in the inspiratory and expiratory cough drive (esophageal pressures and EMG amplitudes), inspiratory phase duration (CTI), total cough cycle duration, and the duration of all cough related EMGs (Tactive). When the cough volume was delivered (via the ventilator) during the first half of inspiratory period (at CTI/2-early over inflation), there was a significant reduction in the inspiratory and expiratory EMG amplitude, peak inspiratory esophageal pressure, CTI, and the overlap between inspiratory and expiratory EMG activity. Additionally, there was significant increase in the interval between the maximum inspiratory and expiratory EMG activity and the active portion of the expiratory phase (CTE1). Control inflations coughs and control coughs with additional expiratory resistance had increased maximum expiratory esophageal pressure and prolonged CTE1, the duration of cough abdominal activity, and Tactive. There was no significant difference in control coughing and/or control coughing when sham ventilation was employed. In conclusion, modified lung inflations during coughing and/or additional expiratory airflow resistance altered the spatio-temporal features of cough motor pattern via the volume related feedback mechanism similar to that in breathing., (Copyright © 2016. Published by Elsevier B.V.)

Background: Numerous studies show higher cough reflex sensitivity (CRS) and cough outcomes in children compared to adults and in females compared to males. Despite close link that exists between cough and environment the potential influence of environmental air pollution on age- and gender -related differences in cough has not been studied yet., Purpose: The purpose of our study was to analyse whether the effects of exposure to environmental tobacco smoke (ETS) from parental smoking and PM10 from living in urban area are implied in age- and gender-related differences in cough outcomes of healthy, non-asthmatic children. Assessment of CRS using capsaicin and incidence of dry and wet cough was performed in 290 children (mean age 13.3 ± 2.6 years (138 females/152 males)., Results: CRS was significantly higher in girls exposed to ETS [22.3 μmol/l (9.8-50.2 μmol/l)] compared to not exposed girls [79.9 μmol/l (56.4-112.2 μmol/l), p = 0.02] as well as compared to exposed boys [121.4 μmol/l (58.2-253.1 μmol/l), p = 0.01]. Incidence of dry cough lasting more than 3 weeks was significantly higher in exposed compared to not exposed girls. CRS was significantly higher in school-aged girls living in urban area [22.0 μmol/l (10.6-45.6 μmol/l)] compared to school-aged girls living in rural area [215.9 μmol/l (87.3-533.4 μmol/l); p = 0.003], as well as compared to teenage girls living in urban area [108.8 μmol/l (68.7-172.9 μmol/l); p = 0.007]. No CRS differences were found between urban and rural boys when controlled for age group. No CRS differences were found between school-aged and teenage boys when controlled for living area., Conclusions: Our results have shown that the effect of ETS on CRS was gender specific, linked to female gender and the effect of PM10 on CRS was both gender and age specific, related to female gender and school-age. We suggest that age and gender related differences in incidence of cough and CRS might be, at least partially, ascribed to the effect of environmental pollutants. The role of age and gender in the effect of air pollution on cough strongly suggest some interplay of development with biological and behavioral factors.

The cough reflex is modulated throughout growth and development. Cough-but not expiration reflex-appears to be absent at birth, but increases with maturation. Thus, acute cough is the most frequent respiratory symptom during the first few years of life. Later on, the pubertal development seems to play a significant role in changing of the cough threshold during childhood and adolescence resulting in sex-related differences in cough reflex sensitivity in adulthood. Asthma is the major cause of chronic cough in children. Prolonged acute cough is usually related to the long-lasting effects of a previous viral airway infection or to the particular entity called protracted bacterial bronchitis. Cough pointers and type may orient toward specific etiologies, such as barking cough in croup or tracheomalacia, paroxystic whooping cough in Pertussis. Cough is productive in protracted bacterial bronchitis, sinusitis or bronchiectasis. Cough is usually associated with wheeze or dyspnea on exertion in asthma; however, it may be the sole symptom in cough variant asthma. Thus, pediatric cough has particularities differentiating it from adult cough, so the approach and management should be developmentally specific.

Studies in healthy adult volunteers and patients with chronic cough have shown that women have increased cough sensitivity to inhaled tussigenic stimuli, including capsaicin. The explanation for this phenomenon remains unknown, although the influence of pubertal changes (dimensional, hormonal) may play a role. In the present study we set out to examine the effect of the pubertal status on cough reflex sensitivity in a population of male and female children and adolescents. The study consisted of cough reflex sensitivity (CRS) testing, spirometry, and a children-completed pubertal status questionnaire. The inclusion criteria were no current symptoms of respiratory disease, no respiratory infection in the preceding 2 weeks, no allergic disease, and no other disease that could modulate CRS. All children were non-smokers. For assessing the CRS we used a compressed air-driven nebuliser controlled by a dosimeter with an inspiratory flow regulator valve. Each subject inhaled up to 12 capsaicin aerosol concentrations (0.61-1250 micromol/l) during 400 ms at 1 min intervals. CRS was defined as the lowest capsaicin concentration that evoked minimally 2 coughs. 225 children (median age 13 yr, 103 girls/122 boys) were divided according to the pubertal status (prepubertal, early pubertal, and late pubertal) and gender. We found that CRS [geometric mean (95%CI)] was similar in prepubertal and early pubertal girls and boys. However, CRS was significantly higher in late pubertal girls (n=56) than in boys (n=26) [53.57 (35.62-80.64) micromol/l vs. 119.7 (70.74-208.55) micromol/l; respectively; P=0.017]. We conclude that puberty and gender have a significant influence on the cough threshold to capsaicin. It seems, however, hard to determine what factors are responsible for the observed gender differences in cough reactivity adolescents.

Experimental and clinical studies performed in adults revealed that gastresophageal reflux disease (GORD) is associated with an appreciable increase in cough reflex sensitivity (CRS). The association between respiratory diseases and GORD is also present in children, but there is little evidence that GORD without aspiration of refluxate (proximal reflux) is a frequent cause of cough in children. The aim of this study was to find out whether CRS in children with GORD will be changed compared with healthy children, and if so, to determine the role of proximal vs. distal reflux in these changes. CRS and 24-h esophageal pH monitoring were performed in 20 children of whom 13 had confirmed GORD and 7 were suspected to have GORD. The control group consisted of 27 healthy children. For assessing the CRS, each subject inhaled 12 capsaicin aerosol concentrations (0.61-1250 micromol/l) at 1 min intervals. CRS was defined as the lowest capsaicin concentration that evoked minimally 2 coughs (C2). CRS in the group of children with suspected GORD [C2: 17.0 micromol/l (6.4-45.6 micromol/l)] and with confirmed GORD [C2: 13.4 micromol/l (3.6-50.9 micromol/l)] were significantly elevated (P<0.05) compared with healthy children [C2: 72.1 micromol/l (25.5-203.9 micromol/l)]. According to the parameters of 24-h pH monitoring, a significantly higher exposure to acid was present in the distal compared with proximal oesophagus. CRS changes correlated negatively with the distal, but not proximal, esophageal acid exposure. In conclusion, CRS changes in children suffering from GORD are similar to those described in adult patients with GORD. It is plausible that the main role in increased CRS in children with GORD play episodes of distal acid refluxes.

Radiotherapy of tumors in the chest and neck regions may have serious pulmonary side effects. It is well known that inflammation is an essential manifestation of radiation-induced injury. This can heal spontaneously, by specific treatment, or it may progress to more intensive inflammation up to irreversible pulmonary fibrosis. To prevent such complications, it would be useful to have a simple non-invasive and sensitive method for monitoring the course of airway and lung post-irradiation inflammation. This study is devoted to search for such a method. We supposed that cough response intensity (CRI) could be one of the methods, which we are looking for. Guinea pigs (Trik strain, n=32) were used in the study. Animals were divided into two subgroups. Animals of a non-untreated (NT) group (n=14; M=7, F=7) were submitted to sham chest irradiation. The animals of a treated (XRT) group (n=18; M=9, F=9) were exposed to a single dose of gamma rays. Cough was provoked by exposure of animals to citric acid aerosol (CA) in gradually increasing concentrations (0.05-1.6M). CRI testing was performed two days before sham/real chest irradiation, than on 1st, 3rd, 10th, 15th, 21st, and 28th days following the day of irradiation. CRI was quantified in each animal by counting the number of coughs induced by all used concentration of CA. We found a significant increase of CRI in the animals of XRT group on 10th and 21st day compared with the NT animals. An increase of CRI also was found inside the XRT group on the 10th day after irradiation compared with the pre-irradiation value of CRI.

Diabetic autonomic neuropathy (DAN) is manifested by dysfunction of one or more organ systems. Its subclinical form (sDAN) can be recognized with the use of noninvasive cardiovascular reflex tests. As the cough reflex is mediated via autonomic nervous system, there is a reason to suppose that it can also be changed due to presence of sDAN. The aim of the present study was to assess cough reflex sensitivity (CRS) in diabetic children with and without sDAN. A CRS test was performed in 35 children suffering from diabetes mellitus type 1 and the results were compared with those from age-matched 27 healthy children. Cough was induced by inhalation of capsaicin aerosol in doubling concentrations (0.61-1250 micromol/l) for 400 ms each. CRS was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2 parameter) and 5 or more coughs (C5 parameter). We found that CRS in the whole group of diabetic children was not significantly different from that in healthy children [diabetic children--C2: 75.1 micromol/l (95% CI: 42.0-134.2 micromol/l)] vs. healthy children--C2: 72.4 micromol/l (95% CI: 75.7-644.8 micromol/l)]. However, a significant decrease (P=0.005) in CRS was found in diabetic children with sDAN [n=12; C2: 221.0 micromol/l (95% CI: 75.7-644.8 micromol/l)] compared with diabetic children without sDAN [(n=23; C2: 42.7 micromol/l (95% CI: 23.1-79.0 micromol/l)]. We conclude that testing cough reflex sensitivity might be a way to establish the presence of diabetic neuropathy.

Context: Retinol-binding protein 4 (RBP4) may play a role in the development of insulin resistance., Objective: We investigated whether RBP4 adipose tissue mRNA expression and plasma level are related to insulin sensitivity during a diet-induced weight loss., Design, Setting, Patients, and Intervention: Obese women followed a dietary intervention composed of a 4-wk very low-calorie diet (VLCD), a 2-month low-calorie diet, and 3-4 months of a weight maintenance (WM) phase., Main Outcome Measures: Clinical investigation was performed before and at the end of each phase. Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp. Adipose tissue mRNA and plasma levels of RBP4 were determined using reverse transcription-quantitative PCR and ELISA, respectively., Results: Weight and fat mass decreased during VLCD and were stabilized during WM. Glucose disposal rate increased during VLCD and remained elevated thereafter. Plasma levels of RBP4 decreased after VLCD and, although increasing at subsequent phases, remained lower than prediet values. Adipose tissue mRNA levels were diminished after VLCD, and increased during low-calorie diet and WM to reach basal values. Basal RBP4 levels or diet-induced variations of RBP4 were not different in lean women and two groups of obese women with high- and low-insulin sensitivity., Conclusions: Severe calorie restriction promotes a reduction in adipose tissue and plasma levels of RBP4. The study does not bring evidence for a role for RBP4 in the regulation of diet-induced changes in insulin sensitivity.

Testing cough reflex sensitivity (CRS) in children requires suitable methodology. A CRS test performed under control of inspiratory flow rate (IFR) shows excellent reliability in children, but it is difficult to perform, especially in younger children. The aim of the present study was to find whether the capsaicin CRS test performed without direct control of constant IFR in healthy children is reliable enough for practical use. The CRS test was performed in 27 healthy children, aged 7-17 yr three times within 8 days. Cough was induced by inhalation of capsaicin aerosol in doubling concentrations (0.61-1250 micromol/l) for 400 ms each. CRS was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Although the intraclass correlation coefficient values showed good to excellent reliability of this test, the within-subject standard deviation values revealed lower reliability of this method compared to the CRS test performed under control of IFR. From the results obtained it is reasonable to conclude that the method using uncontrolled IFR in CRS testing provides acceptable precision only when a bigger sample size is used or more tests are performed. Good to excellent reliability of this method was found in children with higher values of C2 and in those aged 13-17 yr.

It is reasonable to suppose that airway mucosa can be damaged by irradiation applied to chest and neck regions. The inflammatory process is a consequence of an injury. Airway inflammation is one mechanism responsible for cough induction. So, one can suppose that radiotherapy (RT) focused on the patients' chest or neck may injure airway mucosa, which might change sensitivity of the nerve-endings mediating the cough reflex. The purpose of this study was to examine cough reflex sensitivity (CRS) in patients who underwent RT in the chest and neck regions. CRS test using capsaicin was performed in patients with breast cancer (Group A, n=19), and with lung or neck cancer in (Group B, n=14) who underwent RT. Capsaicin aerosol in doubled concentrations (0.49-1000 microM) was inhaled by a single breath. CRS was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Radiation doses ranged from 40 to 70 Gy. Capsaicin cough challenge was performed before and then in the 2(nd) and 5(th) week of RT. We observed a significantly reduced value of C2, i.e., increased cough reflex sensitivity, in Group B in the 2(nd) week of RT (P= 0.04). We conclude that CRS in the lung or neck cancer patients undergoing RT is significantly enhanced, which could result from injury to the nerve endings in airway mucosa.

Thoracic irradiation may cause an acute lymphocytic alveolitis or hypersensitivity pneumonitis. It is well known that cough reflex is sensitized by a number of inflammatory mediators. The purpose of the present study was to investigate the effect of the thoracic irradiation on the cough response in awake guinea pigs. Guinea pigs (Trik strain) were exposed to sham irradiation (n=16), a single irradiation dose of 10 Gy (n=12), and a fractionated irradiation dose (in five fractions) of 15 Gy (n=12) delivered to the thorax. Cough was induced by citric acid aerosol inhalation in gradually increasing concentrations (0.05-1.6 M) during the first week after thoracic irradiation. The cough response was expressed as a total number of coughs induced during all citric acid challenges. Irradiated animals with single dose of 10 Gy exhibited a time- dependent significant increase of citric acid-induced cough in the 6th day after irradiation compared with control animals (P=0.005), whereas cough was not altered significantly in irradiated animals with fractionated dose of 15 Gy. This study demonstrates that the increased cough response may be a determinant of the functional changes of airway nerve-endings mediating cough in the early phase after thoracic irradiation.

We have reviewed the role of afferent inputs and blood chemical changes to the central nervous system, and the way in which they modify the cough and expiration reflexes (CR and ER). Slowly adapting pulmonary stretch receptors (SARs) augment the CR, insofar as when their activity is abolished the CRs from the tracheobronchial (TB) tree and larynx are abolished or weakened. However, stimulation of SARs by lung inflation has an inconsistent effect on the CR. Activation of SARs strongly potentiates the ER from the vocal folds, by a reflex mechanism, and inhibition of SARs weakens the ER. Bronchopulmonary C-fibre receptors inhibit the CR, as do capsaicin-sensitive afferents from the heart and splanchnic bed, cutaneous cold receptors and those that respond to chest wall vibration. Nasal receptors responsive to the irritant agent capsaicin potentiate the reflex. Acute hypoxia also augments the CR, and the reflex is down-regulated by carotid body resection. On the other hand, the CR is inhibited by prolonged hypoxia and hyperoxia, and by hypercapnia. Thus different inputs to the cough-controlling mechanism in the brainstem have very varied effects on the CR. We conclude that the sensitivities of the CR and ER can be modified in a large variety of physiological and clinical conditions, and that there is no clear relationship between the reflexes and changes in breathing caused by the interventions.

Inhalation of high concentration of oxygen produces a lung injury in men and experimental animals. In our previous experiment we have found suppression of cough reflex in healthy guinea pigs after an exposure to 100% O2 for 60 hours. This study was designed to find the effect of hyperoxia on cough reflex in guinea pigs with lungs damaged by bleomycin. We used 48 animals (300-400 g) in two separated experiments. 32 of them were intratracheally injected with 1.5 mg bleomycin (Bleocin, Nippon Kayaku Co., Ltd., Tokyo, Japan) for induction of lung damage according to the method described by Parizada et al (20). 16 animals were given saline, only (control). Animals of experimental group were divided into two subgroups according to the lapse of time from bleomycin application. 13 days after bleomycin application animals of the 1st subgroup (16) were exposed to 100% O2 (8) or to room air (8) for 48 h. Similarly, 20 days after bleomycin application guinea pigs of the 2nd subgroup (16) were exposed to 100% O2 (8) or air (8), respectively. Cough was provoked in conscious animals placed in bodyplethysmograph box by inhalation of citric acid aerosol (0.3 mol/L) before, then 13 or 20 days after bleomycin application, and finally at the end of 48-h exposition to 100% O2 (air). The number of coughs was counted from airflow trace recorded by pneumotachograph. Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anaesthetized animals (Urethane, 1.1 g/kg, i.p.) just after the end of oxygen exposition and was evaluated from the interpleural pressure record. The results have shown a tendency to inhibition of citric acid cough reflex in animals 13 days treated with bleomycin and exposed to 100% O2, and significant decrease in citric acid induced cough in animals 20 days treated with bleomycin and exposed to 100% O2. Significant changes were present in cough intensity induced by mechanical stimulation of TBr region of the guinea pigs airway treated with bleomycin and exposed to oxygen, too. (Tab. 1, Fig. 3, Ref: 29.)

There is a lot of problems related to undergraduate medical education (UME) at Slovak medical schools, e.g. low level co-ordination and integration of curriculum, isolation of teaching subjects, amateurish teaching methods, low level of management, which result in low level of effectivity, late and insufficient reactions to the needs of medical practice. There is urgent need for complex reform of UME if we like to be able to complete with high quality medical schools in Europe. The reform should be focused to the content of curriculum--to integrate preventive and acute medicine into the UME, to improve training of medical students for service in primary health care, to start with renaissance of humanistic education of medical students, to improve research training and teaching of medical informatics. For improving organisation of UME it is necessary to prepare modern profile of graduates from medical school, and from the profile to derive co-ordinated and integrated system of UME. The teachers at medical school should be professionals not only in medical specialization, but in pedagogy, psychology and management, too. Passive forms of education (e.g. lectures) should be partly substituted by active methods, e.g. problem--based learning. More attention should be devoted to elaboration of criteria for evaluation quality of teaching process. The reform of UME have to be done if we like to have a chance to be as good as the best medical schools in Europe. I believe, we want it all! (Ref. 31.)

The cough reflex elicitability (CRE), cough reflex strength (CRS) and Hering-Breuer inflation reflex (HBIR) were studied in 51 anaesthetized (Pentobarbital Spofa, 30 mg/kg, i.v.) female rabbits 24-h and 48-h after SO2 breathing. To provoke cough, the interior of the trachea and carina were stroked with a polyethylene catheter. To elicit the HBIR, the lungs were inflated to 1.0 kPa intratracheal pressure. Intrapleural and systemic blood pressures were recorded. The CRE, CRS and HBIR obtained 24-h and 48-h after SO2 breathing were compared with correspondent values of control animals. It was found, that CRE and HBIR were fully recovered 24-h after SO2 breathing, but the CRS was still decreased, however, there were no significant differences in CRE, CRS and HBIR between animals 48-h after SO2 breathing and control animals. It can be concluded, that decrease of the CRS 24-h after SO2 breathing is not due to slowly adapting stretch receptors block of airways.