Asthma and pregnancy

Pregnancy is accompanied by physiological hyperventilation that may be perceived as shortness of breath; causes are a reduced residual capacity and a reduced expiratory reserve volume due to the swelling uterus, and a larger tidal volume due to increase of the progesterone concentration and of the chemosensitivity to CO2 and O2. Fatigue, lowered exercise tolerance and orthopnoea also may occur, as do basal crepitations at auscultation. In pregnant asthma patients the symptoms may either improve greatly or become aggravated. During an asthma attack the foetus is exposed to hypoxaemia, which may be worsened by a decreased uteroplacental blood circulation in case of maternal alkalosis. Poorly controlled asthma has a stronger adverse effect on the unborn child than the judicious use of anti-asthma drugs. Safe drugs against asthma during pregnancy, around parturition and during breast feeding, are cromoglycic acid and ipratropium; relatively safe drugs are short-acting beta-sympathicomimetics, inhalation corticosteroids and systemic corticosteroids, as well as theophylline from the second trimester; use of long-acting beta-sympathicomimetics is advised against.     

Endogenous skin fluorescence includes bands that may serve as quantitative markers of aging and photoaging

Aging and photoaging cause distinct changes in skin cells and extracellular matrix. Changes in hairless mouse skin as a function of age and chronic UVB exposure were investigated by fluorescence excitation spectroscopy. Fluorescence excitation spectra were measured in vivo, on heat-separated epidermis and dermis, and on extracts of mouse skin to characterize the absorption spectra of the emitting chromophores. Fluorescence excitation spectra obtained in vivo on 6 wk old mouse skin had maxima at 295, 340, and 360 nm; the 295 nm band was the dominant band. Using heat separated tissue, the 295 nm band predominantly originated in the epidermis and the bands at 340 and 360 nm originated in the dermis. The 295 nm band was assigned to tryptophan fluorescence, the 340 nm band to pepsin digestable collagen cross-links fluorescence and the 360 nm band to collagenase digestable collagen cross-links fluorescence. Fluorescence excitation maxima remained unchanged in chronologically aged mice (34-38 wk old), whereas the 295 nm band decreased in intensity with age and the 340 nm band increased in intensity with age. In contrast, fluorescence excitation spectra of chronically UVB exposed mice showed a large increase in the 295 nm band compared with age-matched controls and the bands at 340 and 350 nm were no longer distinct. Two new bands appeared in the chronically exposed mice at 270 nm and at 305 nm. These reproducible changes in skin autofluorescence suggest that aging causes predictable alterations in both epidermal and dermal fluorescence, whereas chronic UV exposure induces the appearance of new fluorphores.     

Anatomic orthotopic heart transplantation: the surgical characteristics and the advantages of the method

Standard technique of establishment of interatrial anastomoses allows to carry out orthotopic transplantation of the heart quickly and reliably. However the accumulation of collective experience evidences about a number of unavoidable shortcomings of such operation: rhythm disturbances, worsening of hemodynamics in discordant atrial contractions of recipient and donor, atrio-ventricular valve insufficiency, thromboembolism, coronary fistulas. Since 1990 in RRCS 25 operations were carried out with the use of standard technique and we also met with the risk of developing the above complications. In experiment on 30 mongrel dogs the technique of anatomical, truly orthotopic transplantation of the heart with six anastomoses was developed: left pulmonary veins with a common cuff, separate anastomoses of the superior and inferior caval veins, anastomoses of aorta and pulmonary artery. Particular attention was paid to developing of original surgical modes for prophylaxis of stenoses in the area of anastomoses of pulmonary and caval veins. In 1997 the anatomical technique of heart transplantation was successfully introduced by us into clinical practice. Clinical electrophysiological, echocardiographic and functional examinations have confirmed the results of the experiments and have evidenced for substantial advantages of the anatomical technique of orthotopic transplantation of the heart. By reliability the new operation is not inferior to standard method of N. Shumway.     

Mammotrophic activity in rat serum during the oestrous cycle, pregnancy and lactation

The mammotrophic activity of various serum samples was assessed on the mammary gland of pregnant rats, in organ culture. Insulin was added to the medium. Serum samples from virgin rats showed little activity, and variation in mammotrophic activity during the oestrous cycle was slight. During pregnancy a significant increase in proliferative activity was not seen during the first week, but around day 8-9 mammotrophic activity increased sharply. The activity showed maxima around days 12 and 19. A decrease in the activity between these maxima was not consistently observed. Mammotrophic activity was still present in sera collected during parturition, and 30 min after parturition. It had disappeared completely within 24 h. The mammotrophic factor detectable by organ culture in the serum of pregnant rats could be rat chorionic mammotrophin. Activity in the serum on day 0 and 1 of lactation was comparable to that of virgin rats, but some activity appeared on day 2. High actvities were foound frequently around day 4 to 6 of lactation. On other days the activity showed fluctuations without a definite pattern. Litter size was of minor importance but the combination of a larger litter size and fasting-overnight seemed to suppress the presence of mammotrophic activity in the serum. Nursing was important: after weaning the activity has disappeared, while renewed nursing after weaning resulted in the appearance of high levels of activity. The mitotic activity obtained with lactating rat serum in the culture was suppressed by addition of rabbit anti-rat prolactin serum to the medium. This suggests that the main mammotrophic factor detectable by organ culture in the serum of lactating rats, is prolactin.     

Time sequence and site of fluid accumulation in experimental neurogenic pulmonary edema

The initial phase of pulmonary edema development following intracranial pressure elevation was studied by means of transmission electron microscopy. Using perfusion fixation and application of a blood tracer (HRP horseradish peroxidase) the time sequence and site of fluid leakage out of pulmonary vessels was demonstrated: - passage of edema fluid through intercellular clefts of alveolar capillary endothelium - edema accumulation in alveolar interstitial tissue - draining of edema fluid from the alveolar septum to the interstitium of terminal bronchioli and to lymphatic vessels. An early interepithelial fluid leakage out of the alveolar wall remains questionable.     

Atheroembolic disease following administration of tissue plasminogen activator (TPA)

Atheroembolic disease is an uncommon condition with many interesting manifestations and has been reported following various procedures. Its occurrence following thrombolytic therapy is extremely rare, with only a few case reports in the literature. However, with a widespread application of thrombolysis in patients with acute myocardial infarction, its incidence is likely to increase and therefore this entity needs to be recognized. Early recognition of the illness may help avoid further expensive and unnecessary investigations. We report two cases of atheroembolic disease following the administration of human recombinant tissue plasminogen activator (TPA).     

In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer

Thirteen postmenopausal women with advanced breast cancer were enrolled in an open randomized Phase I trial of a new p.o. active aromatase inhibitor, CGS 20267 (letrozole). The primary aim of the trial was to assess the impact of two doses of letrozole (0.5 and 2. 5 mg/day) on the peripheral aromatization of androstenedione to estrone. An in vivo isotopic technique was used to measure peripheral aromatization in each patient before treatment. The patients were then randomly assigned to one of the two doses, and measurements of aromatization were repeated after 6 weeks. At 0.5 mg and 2.5 mg/day, letrozole inhibited aromatization by 98.4% (97.3 to >99.1) and >98.9% (98.5 to >99.1; geometric means and ranges), respectively. Plasma estrogen levels were also measured before and during treatment. At the dose of 0.5 mg/day estrone and estradiol levels fell by 82.0% and 84.1% (geometric means), respectively. At the dose of 2.5 mg/ day, the estrogens fell by 80.8% and 68.1%, respectively. There were no significant differences between the doses in aromatase inhibition. No formal statistical analysis was performed on the estrogen data. Letrozole is therefore a highly effective inhibitor of aromatase, causing near complete inhibition of the enzyme in peripheral tissues at the doses investigated. The falls in estrogen levels were greater than those seen with earlier generation aromatase inhibitors.