[Prenatal diagnosis from the internal medicine viewpoint].
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Biomedical subjects
Publications and source records attributed to K Derfler.
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EPH-gestosis (pre-eclampsia-eclampsia) characterized by edema, proteinuria and hypertension occurs primarily in the nullipara, usually after the 20th gestational week. As in normal pregnancy there is striking change in both renal blood flow and glomerular filtration rate a slight increase in urinary protein secretion is not considered abnormal until it exceeds 300 mg/day. Abnormal proteinuria commonly accompanies pre-eclampsia and may be minimal, moderate or severe (even exceeding greater than 25 g/l). Proteinuria was typed mainly of nonselective glomerular origin by using the SDS-disc-electrophoresis. Additionally the clearance ratio of IgG to transferrin in all patients with abnormal proteinuria was evaluated. In none of the patients studied the ratio was less than 0.1 (highly selective). As severe proteinuria is associated with fetal growth retardation, preterm deliveries and prenatal mortality the quantitation and typing of early proteinuria is essential for considering patients who are at risk for developing EPH-gestosis.
A patient in second relapse of acute erythroleukemia (AEL) was treated with 10 MU of recombinant interferon (IFN)-alpha subcutaneously for 24 days after he had failed standard chemotherapy. Besides fever up to 38.9 degrees C and a transient raise in liver function parameters, treatment was well tolerated but had to be discontinued because of a severe decrease in white blood cell and platelet count. After termination of IFN treatment, both cell populations showed a continuous rise during the following weeks and hemoglobin increased concomitantly. Partial remission could be reached as was demonstrated by a decrease in PAS-positive erythroblasts in bone marrow biopsy. Further studies with IFN in patients with AEL refractory to cytostatic chemotherapy are recommended.
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Using standard real time sonography, renal cortical echogenicity, renal length, intrarenal cystic structures and renal calculi were evaluated in 63 patients (30 men, 33 women) in end-stage renal parenchymal diseases (glomerulonephritis n = 21, diabetic glomerulosclerosis n = 9, analgesic nephropathy n = 14, chronic atrophic pyelonephritis n = 19). Patients with glomerulonephritis and diabetic glomerulosclerosis presented with larger kidneys and only slightly increased cortical echogenicity as compared to analgesic nephropathy and chronic atrophic pyelonephritis. In addition, intrarenal cystic structures were found in 50% of the patients with analgesic nephropathy and in 31% of the patients with pyelonephritis, compared with only 14% and 11% in patients with glomerulonephritis and diabetic glomerulosclerosis, respectively. Intrarenal calcifications were more frequent in pyelonephritis and analgesic nephropathy. In end-stage renal parenchymal disease, sonography might be able to distinguish between different types of renal medical disorders.
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The successful outcome of a pregnancy complicated by reversible renal failure secondary to total ureteral obstruction caused by a pregnant uterus and treated temporarily with nephrostomy is reported. The cyclosporine A (CsA) and prednisone treated female recipient of a cadaveric renal allograft gave birth to a male child, which at 2080 grams was small for gestational age (35 weeks of pregnancy). The child presented neither signs of congenital anomalies or chromosome aberrations nor nephrotoxicity, hepatotoxicity or anemia. Simultaneous measurement of trough CsA blood levels (CsA RIA, Sandoz) displayed reduced values in the child's blood (mother 864 ng/ml-4 hours after oral CsA intake; son 312 ng/ml). Beside postrenal failure the patient's pregnancy was complicated by 7 rejection episodes treated with high doses of methylprednisone (total dose 5 g) with reversible damage of the transplant function, two episodes of a urinary tract infection and increasing anemia necessitating blood transfusions. The HIV negative patient had developed a Kaposi's sarcoma 6 weeks after grafting. The progression of infiltrating skin lesions during pregnancy was not seen.
In 5 cases with minimal change nephritis Cyclosporine A has been added to the conventional steroid therapy, when relapse of nephrotic syndrome occurred while reducing the daily prednisolone dose. The intended cyclosporine trough level ranged from 250 ng/ml to 450 ng/ml whole blood, estimated by the RIA method. Proteinuria disappeared in 4 out of the 5 cases, in the other one urinary protein excretion was strikingly reduced. In the 4 cases with complete remission of proteinuria prednisolone was tapered. These patients have cyclosporine A as the sole immunosuppressive drug since 56 weeks and do not show proteinuria. Side effects of cyclosporine therapy have been slight deterioration of kidney function in 2 out of the 5 cases and the occurrence of hypertension in 4 patients.
We report on a 22-year old patient who received a cadaveric renal transplant following haemodialysis treatment for five months due to endstage chronic glomerulonephritis. 14 months after successful transplantation while on stable renal function (serum-creatinine 1.0-1.4 mg%) the patient became pregnant. As an immunosuppressive therapy the patient got cyclosporine A and cortisone. The monitoring of the immunosuppressive therapy (Cyclosporine A) was performed by daily measurement of serum concentration by radioimmunoassay. Drug administration was adjusted to maintain serum levels of 250-550 ng/ml. Increased dosages were required from 25th week until delivery. Until the 25th week of gestation the pregnancy was uncomplicated from both the nephrological and obstetrical points of view. At the 25th week of gestation the patient became anuric. This was caused by a postrenal failure due to the compression of the transplantar ureter by the pregnant uterus. Nephrostomy was installed and was used until the end of pregnancy. In the third trimester the foetus showed growth retardation. For this reason a Caesarean section was necessary at the 36th week of gestation. A healthy boy was delivered weighing 2080 g and measuring 45 cm. No congenital malformations were observed, the chromosomal analysis showed no aberrations. After the delivery cyclosporine concentrations in the blood of the mother and the newborn were simultaneously measured. A remarkable difference in these concentrations was observed particularly in the mother's blood 864 ng/ml whereas in the baby's blood the concentration was 312 ng/ml. Three days after the delivery the patient was able to urinate normally so that the nephrostomy could be removed.
Nephrotoxicity is the main side effect of cyclosporine therapy. In this study 2 groups consisting of 6 kidney transplant recipients were investigated. The oral cyclosporine daily dose was in the first group 13 mg/kg, in the second 11 mg/kg, respectively. In both groups, the daily dose was divided on the first day of investigation in 2 equal portions given at an interval of 12 hours. On the second day, the same dose was divided in 3 equal portions given at an interval of 8 hours. After cyclosporine administration twice a day very high blood cyclosporine peak concentrations (two to three times higher than the therapeutic range) were measured. These potential nephrotoxic cyclosporine concentrations could be prevented by cyclosporine application in 3 equal portions. A reduction of the daily dose in the early period after kidney transplantation to a starting daily dose of 12 mg/kg or even 10 mg/kg can be recommended.
Plasma fibronectin concentrations up to 85 mg/100 ml were found in hyperthyroid patients. There was a significant correlation between free thyroxine index and plasma fibronectin values. Hypothyroid patients had low to normal fibronectin concentrations. Parallel decreases of thyroid hormones and plasma fibronectin concentrations were noted during treatment with thiamazole. A direct effect of thyroid hormones on fibronectin synthesis seems probable.
Blood lymphocyte subpopulations (Leu 4+ cells = pan-T cells, Leu 3a+ cells = helper/inducer cells, and Leu 2a+ cells = suppressor/cytotoxic cells), thyroid-stimulating immunoglobulins, microsomal antibodies and antibodies against thyroglobulin were determined in 10 patients with hyperthyroidism due to single autonomously functioning thyroid nodules (ATN), 11 patients with hyperthyroidism due to Graves' disease (GD) and in 20 normal subjects. Thyroidectomy was performed in 8 of the patients with ATN and in 6 of those with GD after 3 weeks of antithyroid drug treatment with methimazole. Lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T cells as well as B+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal lymphocytes were examined. Blood Leu 4+ cells were reduced due to a lack of Leu 2a+ cells in patients with ATN and GD when compared to normal subjects. Thyroid-stimulating immunoglobulins were detected in all patients with ATN and GD, but in none of the normal subjects. Lymphocytic infiltration of thyroid tissue was present in patients with ATN and GD. The various lymphocyte subsets in the thyroid gland did not differ between the two patient groups. DR expression on thyrocytes was seen in 6 of the patients operated for ATN and in 5 of those who underwent surgery for GD. Infiltration with DR+-T lymphocytes was found in all thyroid glands investigated. Thus immunological findings usually classified as proof for the autoimmune origin of GD exist also in patients with ATN. An overlap in the pathogenetic background of both diseases seems possible.
Myocardial perfusion was studied using Thallium-201 (Tl-201) after dipyridamol in 33 patients on maintenance haemodialysis. It could be shown that coronary artery disease was underestimated by clinical symptoms, 55 per cent of patients had abnormal Tl-201 scintigrams, whereas typical or atypical chest pain was present in only 33 per cent of the patients. Eleven patients died within a year of the scintigraphic study, which resulted in an average mortality rate of 7.7 per cent/year. The risk of developing fatal cardiovascular complications was higher in patients with an abnormal Tl-201 perfusion (7 of 18) than in those with a normal scintigram (1 of 15). Thus nuclear medicine procedures appear to be of diagnostic value in haemodialysis patients, which in addition may have prognostic implications.
The clinical applicability of bone scintigraphy (Tc99m MDP) was evaluated in 42 patients on maintenance hemodialysis. Typical scintigraphic findings are shown which were related to hormonal and biochemical parameters of calcium and phosphate metabolism. Visual grading of representative regions for metabolic bone disease in bone scans was compared to scintimetry which applies a bone to soft tissue ratio to grade osseous abnormalities. It could be shown that visual interpretation and grading of the findings according to a score is sufficient to assess the degree and extent of renal bone disease. Semiquantitative analysis of bone scintigrams by scintimetry did not improve the diagnostic information.
Myocardial perfusion using Tl 201 after dipyridamol was evaluated in 33 patients on maintenance hemodialysis. In addition radionuclide angiography (RNA) was performed following hemodialysis to assess left ventricular function. RNA was done at rest in 31 patients and repeated in 13 after isometric exercise. All patients studied showed no signs of congestive heart failure. 55% of the patients had abnormal Tl 201 scintigrams, whereas coronary artery disease (CAD) was underestimated from clinical symptoms alone (33%). The incidence of an abnormal Tl 201 finding increased with the duration of hemodialysis treatment. However, in the symptomatic patients angina appeared already in the first (45%) or second year of hemodialysis treatment. 39% of patients with abnormal Tl 201 findings died within a year following scintigraphic examination. From 15 patients with normal Tl 201 scans 26% died. Overall mortality rate was above that in asymptomatic or mildly symptomatic patients with CAD, averaging about 7.7% per day. The major causes of death were cardiovascular complications in patients with abnormal Tl 201 findings. In all patients left ventricular ejection fraction (LVEF) was within the normal range following hemodialysis. Thus in our patients LVEF appeared not as an important prognostic characteristic. However, ventricular function can be impaired following exercise. As expected, in 7 patients with CAD (abnormal Tl 201 scan) isometric handgrip induced a mean decrease in LVEF by 11% and abnormalities in regional wall motion. However, also in 4 of 6 patients with normal Tl 201 scintigrams LVEF decreased following isometric exercise.(ABSTRACT TRUNCATED AT 250 WORDS)