Serum enzymes of collagen synthesis and type III procollagen amino-propeptide in Nigerian patients with sickle cell disease

Serum immunoreactive prolyl hydroxylase protein, galactosylhydroxylysyl glucosyltransferase activity and the aminoterminal propeptide of type III procollagen were measured in 20 patients with sickle cell disease and the values were compared with those in 20 apparently healthy Nigerians. The means for the two enzymes and serum aminoterminal propeptide of type III procollagen were significantly higher in the sickle cell disease patients. Significant correlations were found between the values for the two enzymes and the protein serum aminoterminal propeptide of type III procollagen within the sickle cell disease patients. The data confirm that collagen formation is found in the liver, bone and other organs of patients with this disease. The measurement of serum immunoreactive prolyl hydroxylase protein, serum galactosylhydroxylysyl glucosyltransferase activity and serum aminoterminal propeptide of type III procollagen in prospective studies might be helpful in predicting hepatic, bone or diffuse fibrogenesis in sickle cell disease.     

Aminoterminal propeptide of type III procollagen: a marker of disease activity in schistosomal patients.

The serum concentration of aminoterminal propeptide of type III procollagen was measured in 44 Egyptian healthy controls and 29 patients with hepatosplenomegaly originating from endemic areas for schistosomiasis in Egypt. Patients were classified into two main groups according to the histopathological pattern of the liver biopsy: patients with active schistosomal liver fibrosis and patients with inactive schistosomal liver fibrosis. Serum aminoterminal propeptide of type III procollagen levels were elevated in most of patients with active fibrosis but not in those with inactive schistosomiasis. From the present work, it is suggested that aminoterminal propeptide of type III procollagen can be used as a marker for active fibrogenesis in patients with schistosomal liver fibrosis.     

The prognostic value of extracellular matrix component concentrations in serum during treatment of adult respiratory distress syndrome with extracorporeal CO2 removal.

The time-dependent concentrations of hyaluronan, aminoterminal propeptide of type III procollagen, and laminin were determined in sera of 16 patients with severe adult respiratory distress syndrome during treatment with an extracorporeal CO2 removal device. Patients were classified according to lung parameters as responders (n = 10) and non-responders (n = 6) to extracorporeal CO2 removal. At the beginning of treatment strongly elevated serum concentrations of all studied extracellular matrix components were found. During the first 6-11 days of treatment the concentrations of aminoterminal propeptide of type III procollagen and hyaluronan increased further in non-responders but decreased in the majority of responders, while laminin decreased in both groups. No significant correlations were found between the serum concentrations of connective tissue components and the parameters of lung function. By non-parametric analysis of variance, significant differences between responders and non-responders according to treatment time could be established. By analysing the time course of the serum concentrations of hyaluronan and aminoterminal propeptide of type III procollagen, a total differentiation between responders and nonresponders was made possible by the trends of these analytes as early as three days after the start of treatment. The determination of aminoterminal propeptide of type III procollagen and hyaluronan in serum of patients with adult respiratory distress syndrome might therefore have prognostic significance in extracorporeal CO2 removal.     

Radioimmunoassays for type III procollagen amino-terminal peptides in humans

Use of radioimmunoassay for the amino-terminal propeptide of type III procollagen for monitoring fibrotic processes in humans has been frustrating because of the nonparallel relation between results for the standard bovine antigen and human serum samples. In the radioimmunoassays I developed for this propeptide and its monomeric Col 1 domain, based on use of antigens from humans, serum samples generated less-steep inhibition curves than did the standard antigen in the propeptide assay; in the Col 1 assay, however, serum and urine samples both generated inhibition curves having the same slope as that generated with the standard Col 1 peptide. Concentrations of human fragment Col 1 in serum samples as measured with the Col 1 assay were usually double those obtained with the human propeptide assay, which in turn were two- to threefold those obtained with the bovine antigen assay. In control subjects and alcoholic cirrhotics the concentrations of antigen in urine and the daily excretion rates as measured with the assay for human Col 1 exceeded those reported previously. The presence of different antigen forms was demonstrated with both assays by gel-filtration analysis of serum and urine samples. The assay for human Col 1 should be suitable for routine clinical chemical use.     

Altered angiogenesis in preeclampsia: evaluation of a new test system for measuring placental growth factor.

BACKGROUND: Decreased concentrations of the circulating angiogenic factors, free placental growth factor (PLGF) and free vascular endothelial growth factor (VEGF), and increased concentrations of the anti-angiogenic factor, soluble fms-like tyrosine kinase 1 (sFLT-1) have been observed during clinical preeclampsia. We established a new PLGF-ELISA kit for the measurement of PLGF in sera. In the present study, we demonstrated the assay characteristics by measurement of PLGF expression in normal and preeclamptic pregnancies as compared to an established research kit. METHODS: Blood samples were taken from 64 women with singleton uncomplicated pregnancies for longitudinal measurement of PLGF in the course of pregnancy. In 30 preeclamptic patients, serum levels of PLGF and sFLT-1 were measured by Human PLGF-ELISA and Human sVEGF R1 ELISA according to the described test principles. The assay characteristics of the new PLGF-ELISA were determined and the results were compared to those performed with an available research kit. RESULTS: The PLGF concentration in normal pregnancies showed a steady increase starting at the beginning of the second trimester with a peak at 28-32 weeks and a consistent decline thereafter. The preeclamptic pregnancies had significant lower serum concentrations of PLGF and significant higher serum concentrations of sFLT-1 as compared to the non-preeclamptic pregnancies. All the measured assay characteristics fulfilled the required specifications. Comparison of the values of the new PLGF-ELISA and the established research kit resulted in a correlation coefficient of 0.921. CONCLUSIONS: Our results support the hypothesis that an imbalance between factors promoting angiogenesis, such as PLGF, and factors antagonizing angiogenesis, such as sFLT-1, has a fundamental role in the pathogenesis of preeclampsia. The new established ELISA test can be considered reliable and it offers many advantages. As it is authorized for routine diagnostic testing, it may offer new possibilities in the prediction of preeclampsia in clinical routine.     

Hemostatic parameters and platelet activation by flow-cytometry in normal pregnancy: a longitudinal study

Summary Nineteen pregnant women with uncomplicated pregnancies were studied during the first, second, and third trimesters. We measured the following hemostatic parameters: prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C, protein S, platelet number and volume. Platelet function was examined by a cytofluorimetric method, using an anti-GPM-140 antibody which is directed against a platelet α granule membrane protein. Activated platelets were expressed as a percentage of the GMP-140-positive platelets over total platelets. Fibrinogen levels showed a steady increase during pregnancy; conversely prothrombin time, activated partial thromboplastin time, protein C, and antithrombin III showed no significant modifications and remained within the reference range. There was a decrease of protein S activity throughout pregnancy, although protein S antigen did not follow this trend. The decrease occurred early in pregnancy and persisted during the second and third trimesters, reaching a stable plateau. We observed no platelet volume change or activation: the percentage of activated platelets was within the normal reference range, even in late pregnancy.     

初次妊娠高血压综合征患者再次妊娠发生子痫的高危因素

目的:分析初次妊娠高血压综合征(pregnancy-induced hypertension syndrome,PIH)患者再次妊娠发生子痫的高危因素,为临床早期识别和干预高危患者提供参考依据。方法:回顾性分析2016年10月至2018年10月佛山市妇幼保健院初次妊娠确诊PIH的124例孕妇的资料。依据再次妊娠有无子痫分为发生子痫的观察组(n=37)和未发生子痫的对照组(n=87)。记录两组产妇的初次妊娠年龄和孕周、有无PIH或子痫家族史、初次妊娠后高血压有无恢复、两次妊娠间隔时间、再次妊娠的BMI、再次妊娠孕周、两次妊娠血清血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)和胎盘生长因子(placental growth factor,PLGF)的表达水平等资料。采用单因素和多因素logistic回归分析筛选影响初次妊娠PIH患者再次妊娠发生子痫的高危因素。结果:与对照组比较,观察组的家族史、高血压无恢复、两次妊娠期间血清VEGF和PLGF水平均较高(P<0.05),而妊娠间隔时间较短(P<0.05)。多因素logistic回归分析得出:家族史、高血压无恢复、妊娠间隔时间、血清VEGF和PLGF水平均是影响初次妊娠PIH患者再次妊娠发生子痫的高危因素(P<0.05)。结论:具有家族史、初次妊娠后高血压未恢复、妊娠间隔时间较短、两次妊娠期间血清VEGF和PLGF水平较高的初次PIH患者是再次妊娠发生子痫的高危患者,需要早期干预。     

The relation between myocardial cyclic variation of integrated backscatter and serum concentrations of procollagen propeptides in hypertensive patients

Cyclic variation of integrated backscatter (IBS), or CVIBS, provides a noninvasive method to measure myocardial collagen deposition and ischemia in hypertensive patients. We hypothesized that serum procollagen propeptides can offer additional values to CVIBS for evaluating cardiac changes related to fibrosis or ischemia. A total of 21 patients were enrolled in this study and were divided into three groups according to the presence of hypertension and serum carboxyterminal propeptide of type I procollagen (PICP) concentration; these were: 7 hypertensive patients with PICP > or = 127 microg/L (group 1), 7 hypertensive patients with PICP < 127 microg/L (group 2), 7 normotensive subjects with PICP < 127 microg/L (group 3). In addition to PICP, serum aminoterminal propeptide of type III procollagen (PIIINP), stress 201thalium scintigraphy and CVIBS were examined. Phase-compensated amplitudes of CVIBS at mid posterior and mid anteroseptal segments were significantly lower in group 1 (p < 0.05). Patients with fixed 201thallium perfusion defects had lower phase-compensated amplitudes of CVIBS at mid anteroseptal segment and higher PIIINP concentrations (p < 0.05). In conclusions, decrease of myocardial phase-compensated amplitude accompanied with increase of serum PICP concentration may be indicative of the underlying fibrotic process of hypertensive myocardium. Decrease of this CVIBS parameter with increase of serum PIIINP implies concomitant myocardial ischemia.     

Serum oestriol: a parameter of the function of the feto-placental unit (author's transl)]

The determination of serum oestriol is known to be a useful parameter of the function of the feto-placental unit. In order to derive the normal range on application of the radioimmunoassay technique, the serum oestriol level was determined in 242 gravidae during the second half of pregnancy. The pregnancies were all uncomplicated and ended with the delivery of a healthy baby at term. The statistical mean and 4 confidence intervals were calculated for each gestational week individually. During the second half of pregnancy there was a continuous gradual increase in serum oestriol; between the 34th and 38th gestational week there was a further steep increase, followed by a decrease from the 39th gestational week onwards. The usefulness of this method is illustrated on the basis of case reports of 10 high-risk pregnancies in which oestriol determination is compared with the clinical findings and HPL determination.     

Sequential studies of NK cell activity in human pregnancy

We have assessed maternal NK cell function sequentially during and after 14 uncomplicated human pregnancies. As the pattern of response varied in different individuals, a single examination may not provide reliable information. Normally, there was depression of NK cell activity throughout pregnancy, most obvious in the first trimester. In one individual, no depression was seen at any stage. Cryopreservation of peripheral blood leucocytes had no effect on NK activity. In contrast to previous reports, we found no consistent effect of pregnancy serum or plasma on the NK cell activity of control normal lymphocytes.     

Urinary excretion of N-acetyl-beta-D-glucosaminidase in normal and complicated pregnancy

The urinary excretion of N-acetyl-beta-D-glucosaminidase activity, a sensitive indicator of renal tubular injury, was monitored during and after pregnancy. During normal pregnancy, enzymuria increased progressively to levels 3-4 times above normal in the third trimester. In diabetic mothers, enzyme excretion followed a similar pattern, but was generally higher than in uncomplicated pregnancies. Also in preeclampsia, enzymuria tended to be higher than in normal pregnancy. Enzyme excretion normalized about a year after normal pregnancies, but remained elevated in diabetic subjects and in patients who had developed preeclampsia. This latter finding indicates that marginal persistent renal damage may occur during preeclampsia.     

Rapid equilibrium radioimmunoassay for the amino-terminal propeptide of human type III procollagen

This is an equilibrium-type radioimmunoassay for the amino-terminal propeptide of type III procollagen (PIIINP), which overcomes the problem of nonparallelism between the standard and human serum samples encountered with earlier assays. Proper selection of antiserum and reaction conditions diminishes interference from degradation products of the propeptide in serum. Because a rapid solid-phase-bound second-antibody step is included, the assay takes only 3 h. The intra-assay and the interassay CVs are both about 5%. In infants and children the concentration of PIIINP in serum closely parallels the growth-velocity curve. For 88 presumably healthy adults, the PIIINP concentration was 1.7-4.2 micrograms/L, about a third that measured with the previously available commercial assay. This is because of lack of inhibition by small Col 1 domain-related degradation products.     

Beta-Human Chorionic Gonadotropin Levels and the Likelihood of Ectopic Pregnancy in Emergency Department Patients with Abdominal Pain or Vaginal Bleeding

Strategies for diagnosing ectopic pregnancy that defer endovaginal ultrasound in women with suggestive symptoms and serum beta-human chorionic gonadotropin (beta-hCG) levels less than 1500 mIU/mL ignore the increased risk of ectopic pregnancy in these patients. OBJECTIVE: To quantify this increased risk by establishing and comparing the beta-hCG distributions of symptomatic women with ectopic pregnancies, abnormal intrauterine pregnancies, and normal intrauterine pregnancies. METHODS: The authors reviewed the records of a cohort of women who visited an urban emergency department (ED) during a 34-month period with abdominal pain or vaginal bleeding and non-zero quantitative beta-hCG levels. Explicit criteria were used to determine whether the pregnancy ultimately turned out to be intrauterine and normal, intrauterine and abnormal, or ectopic. Probability distributions were compared using frequency distributions, receiver operating characteristic (ROC) curves, and likelihood ratios. RESULTS: Of 730 ED patients included in the analysis, 96 (13%) had ectopic pregnancies, 253 (35%) had abnormal intrauterine pregnancies, and 381 (52%) had normal intrauterine pregnancies. The beta-hCG distributions of patients with ectopic pregnancies and abnormal intrauterine pregnancies were similar and much lower than the beta-hCG distribution of patients with normal intrauterine pregnancies. A beta-hCG level less than 1500 mIU/mL more than doubled the odds of ectopic pregnancy (likelihood ratio = 2.24). Of the 158 patients with beta-hCG below 1500 mIU/mL, 40 (25%; 95% confidence interval [CI] = 19% to 32%) had ectopic pregnancies, and only 25 (16%; CI = 11% to 22%) had normal intrauterine pregnancies. CONCLUSIONS: In women with pain or bleeding and serum beta-hCG levels less than 1500 mIU/mL, the risk of ectopic pregnancy is substantially increased, while the likelihood of normal intrauterine pregnancy is low.     

Longitudinal assessment of changes in reproductive hormones during normal pregnancy

The concentrations of hormones measured in serum from maternal blood change dramatically during pregnancy. While the relative contributions of sex steroids shift from maternal ovaries and adrenals to the fetoplacental unit, other maternal tissues such as pituitary and liver respond to increasing concentrations of estrogen and secrete increasing amounts of prolactin and sex-hormone-binding globulin. To determine longitudinal changes in circulating maternal hormones, we collected blood from 60 women on three occasions during their pregnancies. We observed a 1.7-fold increase in testosterone concentration in serum; concentrations of sex-hormone-binding globulin in serum rose 5.6-fold. The major increase (6.8-fold) in estradiol in serum occurred within the first 16 weeks, followed by a further 4.8-fold increase by term. Mean concentrations of progesterone, 17-hydroxyprogesterone, and androstenedione in serum increased 11.9-, 3-, and 1.3-fold, respectively, whereas concentrations of dehydroepiandrosterone sulfate (DHEAS) fell by 50%. Mean serum prolactin concentrations increased 3.8-fold during the first trimester and by a similar amount during the final 24 weeks of pregnancy. We used these data, obtained from a cohort of women with uncomplicated pregnancies, to construct reference intervals for hormones in maternal serum.     

Serial determinations of the amino-terminal peptide of type III procollagen in severe chronic active hepatitis

To evaluate the diagnostic significance of the amino-terminal propeptide of procollagen type III (P-III-P) in monitoring chronic liver disease, serum P-III-P concentrations were measured in 46 patients with severe chronic active hepatitis (CAH) at entry and at remission during a therapeutic clinical trial. Coded sera were analyzed for P-III-P concentrations by both a standard radioimmunoassay and a recently developed and potentially more precise radioimmunoassay that uses Fab fragments rather than intact antibodies for binding antigen. As compared with conditions in 22 normal controls, P-III-P concentrations were elevated in 98% and 72% of patients with CAH by use of the standard and Fab radioimmunoassays, respectively. With treatment, P-III-P levels fell at remission to levels that were not significantly different from control values, as measured by both assays. The Fab radioimmunoassay, either alone or combined with the standard radioimmunoassay, provided no advantage over the standard radioimmunoassay alone. Serum P-III-P levels, as measured by either assay, correlated poorly or not at all with standard liver function tests and with histologic grade of disease. These data suggest that P-III-P serum levels are abnormal in severe CAH but normalize when remission of disease has been achieved. Consequently, serum P-III-P levels may be a diagnostic aid in the sequential evaluation of patients with severe CAH requiring treatment, and this test deserves further investigation. In this regard, the standard P-III-P assay has greater diagnostic accuracy than the Fab assay.(ABSTRACT TRUNCATED AT 250 WORDS)     

Doppler ultrasonographic evaluation of abnormal pregnancies in the first trimester

Doppler examination of uteroplacental vessels was performed in the first trimester of pregnancy in 111 women with a normal pregnancy outcome and in 10 women with pregnancies that had or subsequently failed due to anembryonic pregnancy (N = 4), missed abortion (N = 1), subsequent spontaneous abortion of live fetus (N = 2), and ectopic pregnancy (N = 3). Flow velocity waveforms (FVWs) were obtained three times by the same observer from subplacental vessels just within the myometrium. The Resistance Index (RI) of the FVWs was compared with the values obtained from 73 uncomplicated pregnancies and 38 women with threatened miscarriage and normal outcome. There was no apparent difference in the values for RI in the 10 patients whose pregnancies had failed, although the 3 live ectopic pregnancies studied had higher values. Although these studies may improve our understanding of the pathophysiology of early placentation, they are unlikely to be of value in the diagnosis of early pregnancy failure.     

Pregnancy and labor after adjustable gastric banding for therapy of morbid obesity

Surgical placement of an adjustable gastric band has become a widely used method for treatment of morbid obesity. As a consequence, a higher number of pregnancies after weight loss is observed. Information is limited on pregnancy outcome after gastric banding, whereas metabolic and nutritional complications are reported after gastric bypass procedures. We report on two cases of pregnancy after laparoscopic gastric banding. Both patients had uncomplicated full-term pregnancies. In both cases, neither during nor after the pregnancy fluid removal from the gastric band was necessary. There seems to be a low probability for gestational and metabolic complications in pregnancy due to gastric banding. However, more specific information about pregnancies and fetal outcomes after gastric banding in a larger patient population would be desirable.     

Connective tissue response to major surgery and postoperative infection

Type I and type III collagen are components of a healing wound, and major structural proteins. According to our previous study, wound fluid concentrations of the liberated propeptide extensions of procollagens can be used to monitor collagen synthesis in the wound. Serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied here for up to half a year in 102 patients, admitted for major abdominal surgery. In a frequent follow-up (n = 9), one minimum and two maxima were found for S-PICP, occurring 1 day, 7 days, and 2 months after surgery, respectively. S-PIIINP had a minimum at 1 day and a peak at 10 days. Relative changes (follow-up result/pre-operative concentration) of the propeptides in 50 uncomplicated patients were compared. The 1-day minimum of S-PICP was 0.60 (SD 0.18), and that of S-PIIINP 0.89 (0.27), (P less than 0.0001, 95% CI for the mean difference 0.21 to 0.36). The 7-day peak of S-PICP was 1.4 (0.5), and that of S-PIIINP 2.5 (1.2), (P less than 0.0001, CI 0.81 to 1.42). The 2-month-peak of S-PICP was 1.6 (0.3), and at the same time the relative S-PIIINP was still 1.7 (0.3) without any separate peak. Major infectious (n = 8) and other (12) complications, exploratory procedures (22) and patients with abnormal pre-operative propeptide levels (8) were studied separately. Two early deaths were excluded. Only major infection had a remarkable effect on the responses of S-PICP (3/8) and S-PIIINP (5/8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetal lung development in pregnancies of diabetic women assessed by quantitative ultrasonic tissue characterization.

OBJECTIVES: This study was performed to compare quantitative ultrasonic tissue characterization of the fetal lung at different gestational ages in uncontrolled diabetic patients with that in normal uncomplicated pregnancies. METHODS: A total of 44 women at 24-37 weeks' gestation with the diagnosis of diabetes in pregnancy were enrolled. Data were compared to those of the control group, which consisted of 140 women with uncomplicated pregnancies of the same gestational age. Longitudinal and transverse sections of the fetal thorax and upper abdomen were examined. A region of interest of constant size was defined and the tissue-specific gray scale was determined by using interactive software. RESULTS: Compared with normal pregnancies, fetal lungs of diabetic pregnancies have a higher echogenicity between 28 and 37 weeks of gestation. The lung mean gray values (MGV) only differed significantly between 30 and 31 weeks of gestation in the group with diabetes (P = 0.033) compared to the control group. The MGV of the liver in diabetic and normal pregnancies is similar during pregnancy, significant differences being found only at 30-31 weeks of gestation (P = 0.038). The lung-to-liver ratio in the control group showed a significant increase from 24 to 31 weeks and a slight non-significant decrease after 31 weeks. The ratio in the group with diabetes increased slightly up to week 33 and decreased slightly afterwards. CONCLUSION: Fetal lung MGV in uncontrolled diabetic pregnancies compared to that in uncomplicated pregnancies differs significantly only between 30 and 31 weeks of gestation.     

Classification of tubal gestations by transvaginal sonography.

Transvaginal sonographic images of tubal pregnancies were correlated with the surgical findings in 191 patients having this condition. The sonographic appearance of the ectopic gestations was classified by the absence or presence of structures such as a 'tubal ring' containing the yolk sac, embryonic structures, heart activity, a sonolucent or irregularly echogenic gestational sac, dilated Fallopian tube with amorphous content, fluid in the pelvis and an empty uterus. The following classifications were made: Type Ia (n = 43) A well-defined 'tubal ring' and a beating heart with or without discrete embryonic or extra-embryonic structures.Type Ib (n = 48) A 'tubal ring' containing embryonic and/or extra-embryonic structures without heart beats. Type II (n = 64) An ill-defined or thin tubal wall containing sonolucent or an irregularly echogenic core but not embryonic or extra-embryonic structures. Type III (n = 28) Free pelvic fluid and an empty uterus in patients with positive serum beta-hCG levels. The outline of the tube cannot be visualized. Surgery revealed unruptured tubal pregnancies in 90 patients of the combined groups of Types Ia and Ib. In one additional patient, a tubal rupture was found. In the Type II patients, 26 tubal pregnancies with blood clots in the tube but no evidence of bleeding into the pelvis, and 38 tubal ruptures or abortions were diagnosed. All Type III patients had ruptured tubal pregnancies or bleeding tubal abortions. In eight patients (4.2%), the only sonographic finding was an empty uterus, and these cases were erroneously diagnosed as not having an ectopic pregnancy (false negatives). There were two false-positive cases in which a tubal ring was detected, and this was related to an hemorrhagic corpus luteum. When used for diagnosing tubal pregnancy, the transvaginal scanning technique (together with beta-hCG in Type III cases) carries a sensitivity of 95.8% and specificity of 99.9%. It is an invaluable tool in the diagnostic work-up and management of patients with suspected ectopic gestation.