Leucylglycinamide released from oxytocin by human uterine enzyme.

Uteri of pregnant and nonpregnant women contain enzymic activities which inactivate oxytocin. A potent enzyme, which has been partially purified from uterine homogenates, cleaves the prolyl-leucyl peptide bond of oxytocin. This findinig associates for the first time the release of the dipeptide leucylglycinamide with the degradation of neurohypophyseal hormones.

Scanning (SEM) and transmission (TEM) electron-microscopic studies on post-ischemic endothelial lesions following recirculation.

The endothelial surface of the vessel wall was studied after various period of recirculation following transitory mechanical hypoxia. The acute changes consisted of partial or total destruction of the endothelium in certain areas. Later on, the regeneration (division and process-formation) of endothelial cells took place over the damaged areas. These events were demonstrated both by transmission and scanning electron microscopy. When severe vessel damage occurred, the subendothelial matrix, collagen and elastic fibres, and the stomata were also set free. Blood cells anchored to these areas were later covered by endothelium. Regeneration was practically complete after 10 days; previously only some small endothelial processes had shown evidence of regenerative activity. In spite of the extensive damage to the endothelium, no occluding thrombus formation was seen. The phagocytes functioned only in removing debris, and the thrombocytes in facilitating endothelial overgrowth.

Biomechanical properties of normal and fibrosclerotic human cerebral arteries.

Quasi-static passive mechanical properties of histologically fibrosclerotic and normal groups of human anterior cerebral arteries (ACA) and internal carotid arteries (ICA) were studied in vivo. Cylindrical arterial segments were subjected to slow, cyclic inflation by air in the range of 5-250 mm Hg intraluminal pressure at axial isometry. To characterize mechanical properties, incremental elastic modulus, incremental distensibility and strain energy density were computed from the continuously recorded pressure-external diameter curves. Compared to normal arteries, at identical intraluminal pressures, the elastic modulus of fibrosclerotic arteries was found to be 34-45% lower in ACA and 40-56% lower in ICA, and the radius to wall thickness ratio was 25-30% smaller in ACA and 37-38% smaller in ICA. Distensibility of fibrosclerotic arteries was not smaller than that of the normal vessels. There were no significant differences in internal radius and in strain energy density between the fibrosclerotic and normal groups. Results of mathematical modelling suggests that the observed decrease in the elastic modulus of fibrosclerotic arteries was accompanied by different types of structural reorganization in the case of ACA and ICA. It is supposed that changes in mechanical properties of the passive wall elements have a compensatory character to restore some hemodynamically important properties of fibrosclerotic arteries, namely tangential stress, incremental distensibility or characteristic impedance.

Prenatal cytogenetic diagnosis: first 1,000 successful cases.

From February 1969 to August 1976, we studied 1,048 amniotic fluids. Of these, 958 (91.4%) were primarily for prenatal cytogenetic diagnosis. Cytogenetic studies were attempted in 1,021 cases; the diagnosis was successful in 1,000 of these. The failure rate of obtaining a diagnosis from the amniotic fluid cell culture of the first amniocentesis was 5% (50 cases); 29 cases had a repeat tap and successful diagnosis was achieved in all. In 21 cases, a repeat tap was refused. Thus, the overall failure rate of obtaining a final cytogenetic diagnosis was 2.06% (21/1,021). There were 32 fetal losses after amniocentesis including 16 spontaneous second trimester abortions, 7 fetal deaths in utero and 9 stillbirths. In two additional cases, fetal death had occurred before amniocentesis. This number of fetal losses does not exceed the number that would be expected in the same maternal age group without amniocentesis. In our series, the frequencies of trisomy in maternal age groups 40 years and over, 37-39 years, 35-36 years, and under 35 years were 4.5, 3.14, 0 and 0% respectively. These frequencies are comparable to those reported from other prospective prenatal studies and higher than those of retrospective live born studies. Various problems and pitfalls in prenatal cytogenetic diagnosis are discussed.

Prenatal diagnosis of renal anomalies.

Within the past 24 months, we have performed prenatal diagnostic studies in 4 pregnancies known to be at risk for well-described genetic syndrome involving renal abnormalities, ie, Meckel syndrome, Roberts syndrome, and bilateral renal agenesis. The diagnostic techniques utilized were ultrasonographic scanning (B-mode and grey scale), biochemical assays, and radiographic evaluation. The ultrasound finding common to the 3 affected cases was extreme oligohydramnios, which we considered indirect evidence that renal anomalies were present. The ultrasound scans of the fetuses affected with Meckel and Roberts syndrome demonstrated anechoic cystic spaces in the abdomen, representing the enlarged dysplastic cystic kidneys. An encephalocele was well demonstrated by B-mode scan in the fetus with Meckel syndrome. The absence of normal limbs in the Roberts syndrome was evident on serial grey scale scans of the fetus. Biochemical and radiographic studies provided results consistent with the suspected diagnoses. The importance of providing genetic counseling and prenatal diagnosis to families at risk is emphasized.

The role of progestationally regulated stromal cell tissue factor and type-1 plasminogen activator inhibitor (PAI-1) in endometrial hemostasis and menstruation.

The physiologic mechanisms whereby the human endometrium maintains hemostasis during endovascular trophoblast invasion, yet permits menstrual hemorrhage, are unknown. This paradoxical relationship was investigated by evaluating endometrial expression of tissue factor (TF), the primary initiator of hemostasis, and plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of fibrinolysis. We observed increased immunostaining for TF and PAI-1 in sections of decidualized stromal cells from luteal phase and gestational endometrium. To determine whether TF and PAI-1 expression are directly linked to decidualization, both endpoints were monitored in a well described in vitro model of decidualization. Thus, confluent stromal cell cultures were exposed to vehicle control, 10(-8) M estradiol (E2), 10(-8) to 10(-6) M medroxyprogesterone acetate (MPA) or both E2 + MPA for 2-24 days in serum-containing or defined media. The progestin enhanced the content of stromal cell-associated immunoreactive and functionally active TF and PAI-1 released into the medium and elevated levels of stromal cell TF and PAI-1 mRNA. While E2 alone was ineffective, it greatly augmented MPA-enhanced TF and PAI-1 protein and mRNA content. Dose-dependent effects on TF and PAI-1 content were observed between 10(-8) to 10(-6) M MPA +/- E2. Similar results were observed for decidual cells derived from first trimester endometrium and cultured in type 1 collagen gels. Following optimal induction of TF and PAI-1 expression by E2 + MPA in stromal cell cultures, removal of these steroids greatly reduced levels of both TF and PAI-1 protein and mRNA within 4 days. These studies suggest a mechanism whereby endometrial hemostasis is maintained during trophoblast invasion yet reduced at the end of nonfertile cycles to permit menses.

The preventability of "bloody taps" in second trimester amniocentesis by ultrasound scanning.

In 856 patients over a 6-year period, amniocentesis was performed in the midtrimester for prenatal genetic counseling. The use of ultrasound scanning of the gravid uterus prior to the procedure reduced the incidence of bloody taps threefold and the withdrawal of grossly bloody amniotic fluid by fourfold. The best results (7.6% overall and 2.0% grossly bloody taps) were obtained when the procedure was performed by an operator not only experienced and adept at intrauterine manipulation but who had training and experience in ultrasonography as well. These results contrast favorably with that of operators utilizing but not trained in ultrasound scanning (36% overall, 8% grossly bloody taps) and of those who had the uterus "mapped out" by a sonographist but performed the amniocentesis later in their offices (18% overall, 12.1% grossly bloody taps). Other advantages of prior sonography are also discussed.

Diagnosing amnionicity at 6 weeks of pregnancy with transvaginal three-dimensional ultrasonography: case report.

OBJECTIVE: To report a case of monochorionic, diamniotic twin pregnancy diagnosed at 6 weeks of pregnancy with three-dimensional (3D) transvaginal sonography and to discuss the use of this diagnostic method in the evaluation of multifetal pregnancy in the first trimester. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A 30-year-old ovum recipient underwent ultrasonographic evaluation of a first-trimester twin pregnancy. INTERVENTION(S): Two-dimensional (2D) and 3D transvaginal sonography. MAIN OUTCOME MEASURE(S): Accurate diagnosis of chorionicity and amnionicity. RESULT(S): Monoamniotic pregnancy and conjoined twinning could not be ruled out by using 2D transvaginal sonography at 6 weeks, because only one yolk sac (YS) and no membranes could be visualized, and the two embryos were closely positioned within one gestational sac. Applying 3D technique, two YSs and two separate embryos could clearly be observed, establishing the correct diagnosis of a monochorionic, diamniotic pregnancy. CONCLUSION(S): The 3D transvaginal ultrasonography provides a quick and accurate diagnostic modality for the evaluation of a first-trimester multiple gestation.

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

Cellular autofluorescent pigment and interstitial fibrosis in smoker's lung.

The mechanisms by which cigarette smoking lead to bronchopulmonary diseases are incompletely understood. The most characteristic lesion is a chronic macrophage-alveolitis accompanied by slight fibrosis and emphysema. The macrophages contain a ceroid-like granular autofluorescent pigment in their lysosomes. Using immunohistochemical methods, open lung-, transbronchial biopsies and cells obtained by broncho-alveolar lavage from cigarette smokers were studied: anti-human macrophage serum and anti-human elastase, immune sera against type I, type III collagens and fibronectin were used in the demonstration of the cellular components of alveolitis and the connective tissue constituents of fibrosis. The characteristic red-brown autofluorescent pigment of the macrophages was also found in an extra-alveolar location mainly in peribronchial, septal and pleural scars. Similar emission colour occurred focally in the elastic laminae of fibrotic alveoli and sclerotic arteries. Granular fluorescent pigment was found in many bronchial epithelial cells. The epithelial pigmentation was associated with increased transcription of nucleic acid proteins, revealed by colloid silver (AgNOR) reaction. The results suggest that the autofluorescent pigment substances in macrophages may indicate or also play a role in the development of pathological connective tissue and epithelial changes of smoker's lung, in addition to the known mediators and enzymes.

Tenascin expression and angiogenesis in breast cancers.

The expression and the distribution of tenascin as well as the extent of blood vessel formation (angiogenesis) were investigated in 70 invasive human breast carcinomas. Formalin-fixed, paraffin-embedded specimens were stained with monoclonal antibody against tenascin-C (DAKO and Biogenex). Anti-CD31 antibody (Biogenex), an acknowledged marker of stromal angiogenesis, was used to detect endothelial cells. Tenascin immunostaining was positive in the tumours around the persisting normal ducts, around tumour-cell nests, in the neostroma, in some tumour cells, and it was found in or around vascular channels. Tumour vascularity was assessed by quantitative vascular grading (Chalkley point count) and was related to the localization and intensity of tenascin immunoreactivity. 19 tumours (27.1%) were scored as low, 35 (50%) as medium, and 16 (22.9%) as having a high vascular grade. The positive correlation between the vascular grade and the tenascin immunopositivity in tumour stroma was observed. Our results suggest that tenascin expression may be associated with endothelial cell activation and may play an important role in tumour angiogenesis.

Connexin 43 expression in rat aortic smooth muscle after ovariectomy and hormonal replacement.

The purpose of this study was to determine the effects of ovariectomy and long-term combined sexual hormone replacement on the gap junctional protein, connexin 43 (Cx43) of aortic medial smooth muscle cells in rats. Twenty non-pregnant mature Wistar female rats were divided into five groups (four animals in each group). Group A underwent ovariectomy, Group B underwent ovariectomy and received estradiol propionate, Group C underwent ovariectomy and received medroxyprogesterone acetate and Group D underwent ovariectomy and received both hormones. Group E was sham-operated and used as control. After 15 weeks of treatment, thoracic aortas were removed and immunohistochemistry was carried out using a specific fluorescent antibody against Cx43. Tissue sections were examined by confocal laser scanning microscopy and analysed by the Scion Image program. All five different groups had the same distribution and extent of Cx43 in the aorta. Neither the ovariectomy nor the hormone replacement had any effect on the Cx43 expression of aortic smooth muscle cells in rats as compared to control animals. These results indicate that sexual steroids do not influence the gap junctional protein Cx43 of the medial layer of aorta in rats. They may suggest that the beneficial effects of estrogen are not mediated via gap junctions in the human aorta either.

Study of inflammatory responses to crocidolite and basalt wool in the rat lung.

The subacute effects of crocidolite and basalt wool dusts were studied by nmeans of biochemical, morphological. and histological methods 1 and .3 mo after intrabronchial instillation. The cell count, protein and phospholipid contents, and lactate dehydrogenase (LDH) activity were determined in the bronchoalveolar lavage (BAL). Both types of fibers induced a prolonged inflammatory reaction in the lung. All the parameters studied in the experimental groups were more markedly elevated after 3 mo. Relative to the control, the protein and LDH values were increased three- to fivefold, the phospholipid content twofold, and the number of free cells in the BAL exceeded the control level up to ninefold. The inflammatory responses to crocidolite and basalt wool in the lung did not differ significantly. In spite of this, basalt wool is recoinmended as an asbestos substitute, as the use of this man-nade fiber may result in a significantly lower release of dust than that from crocidolite.

Use of prostaglandin, hypertonic saline and oxytocin for second-trimester abortion.

The management of second-trimester abortion is still not satisfactory with respect to safety and side-effects; it is considered to be in a state of evolution. The goal of this investigation has been to combine, in reduced quantity, prostaglandin and hypertonic saline in order to minimize the complications and side-effects associated with the separate administration of each component. This study documents the results of a random sample of 385 abortions performed in the second trimester, induced by intra-amniotic instillation of prostaglandin (20 mg) and NaCl 5 and 10 g in different volumes and concentrations augmented with oxytocin. In a series of 20 patients, the coagulation profile is presented and the clinical characteristics of 4 groups are compared. This study demonstrated no coagulation defects. The gastrointestinal side-effects were reduced. In spite of the reduced dosage of each component, the instillation abortion interval still remained 17.08 h on the average. Incomplete abortion ranged from 32% to 48.78%. The data presented in this report suggests that combination of prostaglandin, hypertonic saline and oxytocin is feasible for midtrimester abortion.

PIP: This study was conducted to determine whether combining prostaglandin (PG) and hypertonic saline augmented with oxytocin solution can be used in the management of second-trimester abortion to minimize the complications and side effects associated with the separate administration of each component. A total of 385 2nd-trimester pregnant patients (from the Montefiore Morrissania affiliated hospital and Mount Sinai Hospital of New York City) with gestational age 16 to 24 weeks were assigned randomly to 4 groups: Group 1 (PFG2a 20 mg + 100 ml 5% NaCl injected intraamniotically with no amniotic fluid removed); Group 2 (PGF2a 20 mg + 100 ml 10% NaCL (10g) injected intraamniotically and with no amniotic fluid removed; Group 3 (PGF2a 20 mg + 25 ml 20% NaCl injected intraamniotically and with no amniotic fluid removed; and Group 4 (PGF2a 20 mg + 100 ml 10% NaCL injected intraamniotically and with 100 ml amniotic fluid removed. The standard aseptic transabdominal amniocentesis with an 18-gauge needle and polyethylene catheter was used to administer the abortifacients. Success rate of the procedure was 98.97%. Instillation abortion interval ranged from 15.33 to 20.67 hours (Table 2). Of the 4 dosage schedules, Group 3 exhibited the most satisfactory results, with 15.33 hours as the average instillation abortion interval. Side effects were minimal. This study shows that the combination PG + NaCL augmented by oxytocin is one of the best available approaches to the management of 2nd-trimester abortions. The more amniotic fluid removed, the shorter the instillation abortion interval. Incomplete abortions were between 32 to 48.78%; the incidence was higher in cases where more amniotic fluids were removed.

Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation.

The evaluation of the toxicity of mineral fibres has been tried to achieve in experimental animal models. However, the appearance of fibres in the pleural space could not be explained satisfactorily. Histomorphological examinations showed that intratracheal instillation of asbestos fibres leads to parabronchial and intraalveolar granulomatous tissue reactions and bronchial epithelial regenerations. For further elucidation of the pathogenesis of lung cancer and of mesothelioma the localisation and transport of inhaled fibres is of high interest. Thus, a three dimensional visualization of the structure of rat lungs before and after intratracheal instillation of UICC crocidolite fibres was performed by plastic casts to follow the way of asbestos fibres in the lung tissues and the pleura. The casts allowed to demonstrate airway structures with imprints of epithelial cells and blood vessels of normal and treated animals by scanning electron microscopy. Instilled asbestos fibres transformed bronchial structures and resulted in cystic deformations of the pleural surface. The penetration of single fibres through bronchial trunks and the visceral pleura could be shown for the first time in a three-dimensional topography of the affected tissue. Now, there is support for similar results of histomorphological examinations indicating the possibility that asbestos fibres could penetrate the pleura and migrate into the pleural space. The question if the migration of fibres is a mechanical movement or an active transport is still under discussion.

Rheumatic heart disease diagnosed during pregnancy: a 30-year follow-up.

One hundred one patients originally diagnosed as having rheumatic heart disease (RHD) during the years 1945-1948 were reevaluated in 1975 to determine the natural history of the disease. Twenty patients (19.8%) showed no sign of RHD. Of the patients with confirmed RHD, 56 (70.0%) had their original lesion confirmed, while 23 (28.8%) had developed additional valvular involvement. Pure mitral stenosis resulted in significantly lower mortality than all other valvular lesions, and congestive heart failure was the leading cause of death. Nineteen patients underwent cardiac surgery; the mortality in this group (52.6%) was not significantly higher than that in the overall RHD group (38.8%). False diagnosis of RHD during pregnancy is common. A more thorough evaluation of the "cardiac murmur of pregnancy" is advocated.

A suggested set of working definitions and criteria applicable to induction of labour.

A list of prerequisites, essential items of information and definitions applying to studies on induction of labour is presented. It is suggested that their use would permit proper analysis and comparison of results obtained by different investigators.

Tubular reabsorption of protein by porcine kidneys during neonatal alimentary proteinuria.

The ability of renal proximal tubular cells to reabsorb protein early in postnatal life was investigated using goat haemoglobin as tracer. The haemoglobin was intracardially administered to newborn piglets. The kidneys were fixed for light and electron microscopy 4 h later. Piglets killed immediately after birth and those allowed to suck colostrum for 4 h were used as controls. The proximal tubular cells of newborn, unsuckled piglets already contained absorptive vacuoles. Haemoglobin was absorbed in some absorptive vacuoles of the proximal tubules. The tracer was also demonstrable in the urine, mainly in the form of methaemoglobin. Although proximal tubular cells of newborn piglets are able to absorb protein, this absorption is of limited extent and excess protein is voided with the urine.

[The role of uterine and umbilical artery Doppler velocimetry for the early detection of pathologic pregnancy]. / Az arteria uterina és az arteria umbilicalis Doppler-ultrahangvizsgálatának szerepe a kóros terhesség korai felismerésében.

Pregnancy induced hypertension remains the most frequent reason of maternal and fetal complications. Recent studies of the entire pathophysiology of the abnormal implantation proved association between the impaired placental performance and the reduced uteroplacental circulation. Therefore the Doppler examination of uterine and umbilical blood flow may provide the early recognition of high-risk pregnancies complicated by maternal hypertension and fetal intrauterine growth retardation. The authors endeavor to describe the details and characteristics of uteroplacental haemodynamic changes during the course of physiologic and defective implantation. On the basis of the currently available scientific publications they summarize the role of the uterine and umbilical artery Doppler velocimetry as a screening tool in the detection of the consequences of the impaired uteroplacental perfusion. They conclude that abnormal velocity waveforms obtained from the uterine and umbilical arteries may help to improve the efficacy of the prenatal care and the perinatal outcome as well. The clinical benefits of this screening method will be precisely defined on the basis of further multicenter studies in Hungary.