Bartter's syndrome and pregnancy.
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Biomedical subjects
Publications and source records attributed to J K Thomsen.
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OBJECTIVE: To investigate the prevalence of carcinoma in situ of the testis in a group of oligozoospermic men from infertile couples. DESIGN: A consecutive group of oligozoospermic men from infertile couples were offered bilateral testicular biopsy. The observed prevalence of carcinoma in situ was compared with the expected prevalence of testicular cancer in a corresponding age matched population of Danish men, assuming all untreated cases of carcinoma in situ progress to tumour stage. This calculation was based on data from the Danish Cancer Registry. SUBJECTS: 207 men aged 18-50 years who had sperm density below 10 million/ml in two samples within the previous 2 years or sperm density below 20 million/ml in two samples within the previous 2 years and a history of cryptorchidism or one or two atrophic testicles (orchidometer volume less than 15 cm3), or both. INTERVENTIONS: Bilateral testicular biopsies. MAIN OUTCOME MEASURES: Carcinoma in situ in the biopsy specimen. RESULTS: No case of carcinoma in situ was found among the 207 men. The expected number in a normal age matched population of corresponding size was 0.8. CONCLUSIONS: There is no increase in risk of carcinoma in situ of the testis in moderately oligozoospermic men of couples referred because of infertility.
The phosphate sites in native ovine, caprine, and bovine casein micelles have been analyzed using sequence analysis, mass spectrometric analysis, and solid-state 31P nuclear magnetic resonance spectroscopy. Using a combination of S-ethylcysteine derivatization, sequence analysis, and mass spectrometric analysis, the phosphorylation sites of ovine (SerP151 and SerP168), caprine (SerP151 and SerP168), and bovine (SerP149) caseinomacropeptides have been localized. Various solid-state 31P methods using magic angle spinning have been applied to ascertain the local structure and dynamics of the phosphorylated serine residues and the inorganic calcium phosphates within the micelles. Contributions from the phosphorylated serine residues of kappa-CN, located in the C-terminal portion of the molecule, to the mobile constituents of the micelles were assigned by comparison with 31P nuclear magnetic resonance spectra of purified caseinomacropeptides from the various species in the dissolved state. Comparison of the 31P magic angle spinning nuclear magnetic resonance spectra of ovine, caprine, and bovine casein micelles indicates that the micelles from these species are very similar but not identical.
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Solid-state magic-angle spinning 31P-NMR spectroscopy was used to characterize the structure and composition of native casein micelles. The features of the magic-angle spinning 31P-NMR spectra, including overlapping resonances from mobile/immobile phosphorylated serine residues and inorganic calcium phosphates, have been determined using different experimental techniques and assigned by comparison with spectra of the presumed constituents within the casein micelle. Comparison with 31P-NMR spectra of alpha s1-, alpha s2-, and beta-caseins in dissolved and freeze-dried forms demonstrated that a major fraction of the phosphoserines in these proteins was in an immobilized state within the micelle. Likewise, from 31P-NMR spectra of the C-terminal part of kappa-casein, it was shown that this region of the micelle has a considerable conformational mobility. Finally, magic-angle spinning 31P-NMR spectra for a series of inorganic calcium phosphates and mineralized bone tissue revealed that the micellar inorganic calcium phosphates exhibit structural similarities to hydroxyapatite and hence resemble mineralized bone tissue.
Simultaneously measured cardiac output obtained by thermodilution (TD), transcutaneous suprasternal ultrasonic Doppler (DOP), CO2-rebreathing (CR) and the direct Fick method (FI) were compared in eleven healthy subjects in a supine position (SU), a sitting position (SI), and during sitting exercise at a workload of 50 W (EX). The agreements between the techniques, two by two, were expressed as the bias calculated as the averaged differences between the techniques. Precision was expressed as the standard deviation of the bias. The overall agreement (bias +/- precision) between TD, DOP and CR respectively and FI were 2.3 +/- 1.6, -0.1 +/- 1.4, and -0.2 +/- 1.1 l/min. TD overestimated cardiac output consistently in SU, SI and EX. DOP was in-accurate during EX and agreed well with FI in SU and SI. CR agreed closely with FI in SI and EX, but values were underestimated in SU. The overall agreement between DOP and CR, respectively, and TD were 2.5 +/- 2.2 and 2.6 +/- 1.6 l/min. The overall agreement between DOP and CR was 0.1 +/- 1.6 l/min. In conclusion, TD overestimated cardiac output compared to the other techniques and the poor agreement has to be taken into consideration especially in measures of low values. The precision of DOP and CR against FI seems to be within clinically acceptable limits, and these methods may provide interchangeable alternatives to the invasive Fick method.
Ultrasound scanning of the testes and surgical biopsy were performed in 95 infertile men to evaluate the use of ultrasound in male infertility. Ultrasonic testicular volume was calculated using three measurements and the formula of an ellipsoid, and the ultrasonic texture was evaluated and given a score from 1 to 5, indicating increasing degrees of irregularity. The median score was 3 (range 1-5), which was higher than previously found in normal men (median score 2; range 1-5; P < 0.0001). The ultrasonic texture score was lower in testes with a uniform pattern of 100% spermatogenic tubules compared with the rest, both for the right (P < 0.001) and for the left (P < 0.0005) testis. Texture score was correlated with the number of obliterated tubules for both testes (P < 0.001). The mean ultrasonic testicular volume of the right testis was 10.30 ml, and that of the left 10.26 ml. Both were smaller compared with the findings in normal men (P < 0.0001). Ultrasonic testicular volume was negatively correlated with texture score (P < 0.001). A positive correlation between ultrasonic volume and sperm count was seen (P < 0.001). Sperm count was negatively correlated with texture score if calculated together with data from 119 men from the general population (P < 0.001). The study shows that ultrasonic volume and texture are valuable parameters in the evaluation of infertile men.
The present study investigated the contribution of adrenergic beta 1-receptor stimulation to the cardiovascular and renal effects of low-dose dopamine in eight normal, water-loaded humans. Metoprolol (100 mg) or placebo was administered orally at 08.00 h in a randomized, double-blind fashion on two different days. Renal clearance studies were performed during a 1 h baseline period, two 1 h periods with dopamine infusion (3 micrograms kg-1 min-1), and a 1 h recovery period. Cardiac output was measured by an ultrasonic Doppler method, and lithium clearance (CLLi) was used to estimate proximal tubular outflow. Baseline values of heart rate, systolic pressure and mean arterial pressure decreased with metoprolol compared with placebo, but cardiac output, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were not significantly changed. Metoprolol significantly decreased baseline CLLi and sodium clearance (CLNa) by 19% (P < 0.01) and 34% (P < 0.01), respectively. Metoprolol blunted the dopamine-induced increases in heart rate and systolic pressure, but cardiac output increased to the same extent on both study days by 26% (placebo, P < 0.05) and by 31% (metoprolol, P < 0.01), respectively. With and without metoprolol, dopamine did not significantly change GFR, and the percentage increases in ERPF were similar on the two study days (40% (P < 0.001) and 42% (P < 0.001), respectively). Dopamine increased CLLi and CLNa by 31% (P < 0.01) and 114% (P < 0.01), respectively, with placebo, and by 36% (P < 0.01) and 114% (P < 0.01), respectively, with metoprolol. Values during infusion remained significantly lower with metoprolol compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: The reports on plasma concentrations and physiological function of atrial natriuretic peptide (ANP) during pregnancy are conflicting. In a recent prospective study, including 40 healthy primigravidae, we found a highly significant decrease in the plasma concentration of ANP (p-ANP) during the third trimester and the results indicated that ANP takes part in regulation of blood volume and renal function during pregnancy as in the nonpregnant state. In order to test these results, a study was performed in primigravidae with twin pregnancy to test if the accentuated physiological changes here were followed by a corresponding greater decrease in p-ANP. METHODS: Ten healthy primigravidae with twin pregnancy were examined four times during pregnancy plus 12 weeks after delivery. Each time the following were measured: p-ANP, aldosterone, renin, blood volume (carbon monoxide), cardiac output (Doppler), blood pressure and sodium excretion. Interdependence of the changes in ANP and in the other parameters was tested using Spearman's rank correlation test on the delta (delta)-values (the differences in measurements between investigations). The results were compared to the results obtained during singleton pregnancy using the Mann-Whitney rank sum test. RESULTS: All pregnant values of p-ANP during twin pregnancy were lower than 12 weeks after delivery, p < 0.01. In the 20th, 28th, and 32nd week p-ANP was lower in twin pregnancy than in singleton pregnancy, p < 0.05. There was a negative correlation between changes in p-ANP and changes in: a) blood volume, R = -0.8, p < 0.0001, b) aldosterone, R = -0.66, p < 0.0001, c) renin, R = -0.52, p < 0.01, d) cardiac output, R = -0.68, p < 0.0001. There was a positive correlation between changes in p-ANP and changes in: a) fractional excretion of sodium, R = 0.73, p < 0.0001, and b) total peripheral resistance, R = 0.61, p < 0.0001. CONCLUSION: The results suggest that the competitive relationship between ANP and the renin-aldosterone system in regulating sodium balance and fluid volume is preserved during pregnancy. The vasodilation during pregnancy is not mediated by ANP.
OBJECTIVE: To determine: 1) if 18 mg iron daily is sufficient to cover the iron need during normal pregnancy, and 2) if women, who will not need iron supplementation during pregnancy, can be identified by early screening. DESIGN: In a prospective study the women were randomized to receive either 18 or 100 mg iron daily from the 16th week until delivery. Investigations were performed in the 16th, 30th, and 38th week. SUBJECTS: Healthy nulliparae (n = 43) experiencing a normal singleton pregnancy. Only women with a normal hemoglobin concentration and intact iron stores (S-Ferritin > 15 micrograms/1) in the 16th week were included. VARIABLES: These measurements were done consecutively: 1) the total hemoglobin mass (with carbon monoxide). 2) S-Ferritin, 3) S-Transferrin, 4) S-Iron, 5) red cell indices (hemoglobin concentration, hematocrit, MCV, MCHC). RESULTS: Changes in red cell indices and S-Transferrin were equal in the two groups. There was no significant difference in S-Ferritin in the 16th week. In the 30th week 3 women (14%) in the 100 mg group and 11 (52%) in the 18 mg group had empty iron stores (p < 0.05). The numbers were 1 (5%) and 15 (72%) in the 38th week (p < 0.0001). The increment in total hemoglobin mass was equal in the two groups from the 16th to the 30th week (13% in the 100 mg group and 12% in the 18 mg group). From the 30th to the 38th week the increment in total hemoglobin mass was largest in the 100 mg group (8.1% versus 2.7%, p < 0.05). CONCLUSION: Despite a normal hemoglobin concentration and intact iron stores in the 16th week, an iron supplementation of 18 mg daily is not sufficient to cover the iron need in many pregnant women in the 3rd trimester.
BACKGROUND: Volume regulation and hemodynamic functions change during pregnancy, leading to marked increases in blood volume and cardiac output, peripheral vasodilatation and reduced sensitivity to angiotensin. Atrial natriuretic peptide (ANP) is intimately involved in fluid and sodium homeostasis and exerts marked relaxant activity on vascular smooth muscle pre-contracted with angiotensin. This study was performed to clarify the role of ANP as a regulator of maternal physiology. METHODS: 40 normal primigravidae were examined five times during pregnancy plus 12 weeks after delivery. Each time were measured: ANP, aldosterone, renin, blood volume (carbon monoxide), cardiac output (Doppler), blood pressure and sodium excretion. Interdependence of the changes in ANP and in the other parameters was tested using Spearman's rank correlation test on the delta (delta)-values (the differences between investigations). RESULTS: P-ANP in the 20th week was 11.4 (8.5-18.9) pmol.l-1 (median, 25 and 75 percentiles), the same as 12 weeks after delivery, 11.5 (9.6-15.2) pmol.l-1, and in a non-pregnant control group, 10.4 (9.0-12.5) pmol.l-1 (n = 20). All measurements of P-ANP during the 3rd trimester were lower than in the 20th week and 12 weeks after delivery, p < 0.0001 (Wilcoxon matched-pairs test). There was a negative correlation between changes in P-ANP and changes in: a) blood volume. R = 0.69, p < 0.0001, b) aldosterone, R = 0.58, p < 0.0001, c) renin, R = -0.54, p < 0.001, d) cardiac output, R = 0.61, p < 0.001. There was a positive correlation between changes in P-ANP and changes in: a) fractional excretion of sodium, R = 0.54, p < 0.0001, and b) total peripheral resistance. R = 0.52, p < 0.0001. CONCLUSION: Decrease in p-ANP is one of the mechanisms whereby blood volume is increased and maintained during pregnancy. The competitive relationship between ANP and the renin aldosterone system in regulating sodium balance and fluid volume is preserved during pregnancy. The results substantiate the physiological importance of ANP as a regulator of blood volume. ANP does not function as a vasodilator during pregnancy.
The total amount of circulating haemoglobin was measured in 12 subjects using a direct carbon monoxide (CO)-technique. O2 plus 50 ml CO gas was rebreathed in a small closed system for 10 min. Carboxyhaemoglobin (HbCO)% was measured with a diode-array spectrophotometer before and after the rebreathing. delta HBCO% and the amount of CO in moles (nCO) were used to calculate the total amount of circulating haemoglobin. Blood volume was calculated by dividing this figure with the haemoglobin concentration and plasma volume by multiplying the blood volume with 1-haematocrit. The calculated blood and plasma volumes were compared with the simultaneously measured volumes by 99mTc-labelled erythrocytes, 125I-albumin and T 1824 (Evans Blue). Mean blood volume determined with CO was 4557 ml (3251-6576 ml) compared with 4527 ml (3390-6527 ml) with 99mTc-labelled erythrocytes (r = 0.97). Mean plasma volume by T 1824 was 2895 ml (1972-3658 ml) vs 2898 ml (1815-3714) ml using 125I-albumin, (r = 0.99). The plasma volumes calculated from the blood volumes determined by the erythrocyte-labelling methods were 5-10% lower than those measured with labelled albumin. There was a better correlation between the plasma volumes by the albumin methods and by the CO-technique (r = 0.98 and r = 0.97, respectively) than between the plasma volumes by the albumin methods and by 99mTc-erythrocytes (r = 0.90 and r = 0.87, respectively).
An easy method to measure blood volume is clinically needed. We used carbon monoxide (CO) and the OSM3 to measure circulating hemoglobin and blood volume with the indicator dilution principle. 50 mL of CO was administered into a closed rebreathing system and taken up via the lungs, and the amount of hemoglobin in the blood was calculated from the increase in carboxyhemoglobin fraction after 10 min. Blood volume was calculated by division with the concentration of hemoglobin. We observed that the absorption spectrum of carboxyhemoglobin (COHb) depends on pH and pCO2, which must be controlled when very accurate spectrophotometry is necessary. The bias is 3% COHb per pH unit during calibration of the OSM3, which may be permissible for patients with CO poisoning, but not for the present purpose. With this in mind the method is very accurate, precise and simple.
Atrial natriuretic peptide (ANP) is a recently discovered cardiac hormone involved in blood-volume homeostasis. Known stimulating factors for ANP release are rise in atrial pressures or atrial distension, suggesting that blood volume regulates ANP release. This study was undertaken to test the hypothesis that plasma levels of ANP are high and increase during normal pregnancy secondary to the expanding plasma volume. In a cross-sectional study plasma concentrations of ANP were measured in 99 normal pregnant women at different gestational ages and compared with the values found in an age-matched non-pregnant control group. Mean plasma ANP was already significantly increased in the first trimester as opposed to the non-pregnant women, but despite a continuously expanded plasma volume there was no further increase during pregnancy. Our findings suggest that other factors must interact with plasma volume in regulating plasma ANP during pregnancy.
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The concentration of plasma immunoreactive atrial natriuretic peptide is positively associated with right atrial and pulmonary capillary wedge pressure, suggesting that blood volume and hence atrial pressure govern its release. Expansion of plasma volume is a central physiological adjustment in normal pregnancy. Conversely, pregnancies complicated by pre-eclampsia are associated with a reduction in plasma volume and central venous pressure. A study was therefore undertaken to test the hypothesis that plasma atrial natriuretic peptide concentrations are low in pre-eclampsia owing to deficient secretion. Concentrations of the peptide were measured by a specific radioimmunoassay. The mean plasma immunoreactive atrial natriuretic peptide concentration in healthy pregnant women (n = 22; third trimester) was higher (56 (1 SD 29) ng/l) than in 25 young, non-pregnant controls (37 (19) ng/l). Concentrations in patients suffering from mild pre-eclampsia (n = 9) were higher (127 (60) ng/l) than in normal pregnant women, and in patients with severe pre-eclampsia (n = 6) concentrations were higher still (392 (225) ng/l). Despite failure of plasma volume expansion and low central venous and pulmonary capillary wedge pressures in pre-eclampsia this condition is associated with greatly increased plasma concentrations of plasma immunoreactive atrial natriuretic peptide, which increase still further with the severity of the disease. These findings are clear evidence that atrial pressure may not be the principal determinant of the release of the natriuretic peptide in pre-eclampsia.
Two pulmonary plasmacytomas of different immunologic type, occurring with an interval of 5 years in the same 65-year-old woman are reported. Both displayed identical light chain types, but different heavy chains. The immunoperoxidase staining technique was used. The patient underwent segmental resection, and no evidence of recurrence or multiple myeloma was found 4 years later. Differential diagnoses are discussed, and the importance of immunologic staining is stressed.