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Biomedical subjects

H Kaffarnik

Publications and source records attributed to H Kaffarnik.

At least 19 recordsLinked to original sources

[Incidence and importance of thyroid gland changes in clinical patients].

The thyroid gland of 536 patients of a medical hospital in an iodine deficient area was investigated by ultrasound. According to the sonographic pattern and to the scintigraphic imaging the focal lesions were analysed as micro- or macrofollicular adenomas, autonomous adenomas, cysts and chalk. The prevalence of goitres was 37.7%. The prevalence of goitres was higher in women (45%) than in men (30%). Focal lesions could be observed in 27.6%, equally more often in women (36%) than in men (18.9%). The frequency of focal lesions increased with the age of the patients and with the volume of the thyroid gland. Autonomous adenomas were found three times more often in women than in men. Hyperthyroidism was only observed in patients with nodules larger than 4 cm in diameter. Sonographic screening examinations of the thyroid gland seem to be useful in all patients of a clinic of medicine because of the risk (25%) of iodine contamination by diagnostic measures.

Adolescent

Reduction of nocturnal diuresis and natriuresis during treatment of obstructive sleep apnea (OSA) with nasal continuous positive air pressure (nCPAP) correlates to cGMP excretion.

In ten patients with severe obstructive sleep apnea (OSA) profound changes in renal function could be demonstrated at night during nCPAP therapy. Natriuresis and diuresis decreased by about 50% while creatinine excretion rate and urinary osmolality did not change. We found parallel changes in the excretion of ANP's second messenger cyclic guanosine monophosphate (cGMP) in a dose-response-related manner to natriuresis respectively diuresis. These data are in agreement with recently demonstrated decrease of nocturnal plasma levels of atrial natriuretic peptide (ANP) during nCPAP therapy in apneic patients. This may be an indicator for an increased cardiac volume load during obstructive apnea. The decrease of diuresis, natriuresis and cGMP excretion demonstrate the beneficial effects of nCPAP treatment on the cardiovascular system. Therefore measurements of cGMP excretion may be a useful parameter to assess the cardiovascular function of apneic patients before and during treatment.

Adult

Disturbances in volume regulating hormone system--a key to the pathogenesis of hypertension in obstructive sleep apnea syndrome?

Recent studies about renal function and volume regulating hormones in obstructive sleep apnea (oSAS) indicate complex disturbances in volume homeostasis. Increased nocturnal secretion of atrial natriuretic peptide (ANP) and decreased renin secretion during apnea looks similar to a situation seen during hypervolemia or increased cardiac volume load. Increased venous return induced by pathologically high negative intrathoracic pressure during obstructive apnea may be the cause. Since during wakefulness no true hypervolemia is present, a "pseudohypervolemia" or "central hypervolemia" must exist caused by volume shift from the peripheral to the central compartment during apnea. Since volume homeostasis and blood pressure regulation are complexly connected the question arises whether disturbances in volume homeostasis play a role in the pathogenesis of arterial hypertension in sleep apnea. In a subgroup of hypertensive patients hypertension is salt-sensitive and volume dependent; it is called volume-expanded or low-renin hypertension. An inhibitor of the Na+/K(+)-ATPase acting via the digitalis receptor - called digitalis like factor (DLF) - is regarded as the causative agent for the development of hypertension in these cases. From this background, we were interested in the question whether DLF may be the linkage between disturbances in volume homeostasis and the pathogenesis of hypertension in sleep apnea. We could demonstrate a decrease of nocturnal urinary excretion of DLF during nasal continuous positive air pressure (nCPAP) therapy. Since a positive correlation between changes in diuresis respectively natriuresis and DLF excretion was found, we suggested DLF to be involved in changes of renal function in sleep apnea besides ANP. In 3 patients we measured nocturnal plasma levels of DLF and renin.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor

Lipolytic enzymes of the human pancreas. III. Auxiliary function of lipase in the cholesterol-esterase-dependent oral test on exocrine pancreatic output.

In the oral exocrine pancreatic function test using fluorescein dilaurate, this synthetic substrate attaches primarily to the triglyceride surfaces of the neutral lipids administered as part of the breakfast: these fluorescein dilaurate molecules cannot be attacked by cholesterol esterase. In the course of triglyceride saponification by lipase and colipase, however, the fluorescein dilaurate is liberated and hydrolyzed by cholesterol esterase. The pancreatic function test, therefore, measures the lipolytic activities not merely of cholesterol esterase, but indirectly of lipase, as well.

Bile Acids and Salts

Isoproteins and an isoelectric focusing mutant of human apoprotein serum amyloid A.

On isoelectric focusing of human plasma and subsequent immunoblotting, using antii-human serum amyloid A (SAA) antibodies, a genetic variant of SAA was detected in a family of Turkish origin. All affected members of the family were apparent heterozygotes for the mutant protein, which underwent a charge shift of about one charge unit toward the anode. The variant is likely to be a mutant of the most prominent forms of SAA (SAA1 and SAA2, or SAA1 and SAA1 des Arg). The appearance of a genetic variant of two of the six reported SAA-isoforms in human plasma supports the concept of SAA proteins being products of different genes.

Antibody Formation

Metformin-induced changes in serum lipids, lipoproteins, and apoproteins in non-insulin-dependent diabetes mellitus.

Forty patients with NIDDM and hyperlipoproteinemia were selected for a 12-week double-blind placebo-controlled trial to study the effects of metformin on lipoprotein concentration and composition. A significant decrease occurred in VLDL-apo B and all lipid components of VLDL, indicating a decreased number of circulating VLDL, while LDL-apo B was unchanged. Moreover in VLDL the relative TG content increased, the cholesterol content decreased, while in LDL the TG content decreased and the cholesterol content increased, indicating a change in the particle distribution over the spectrum VLDL-IDL-LDL. The initially enhanced TG-content in HDL was reduced. While a reduction in VLDL is observed together with improving glucose control irrespective of the applied method, the observed compositional changes in VLDL and LDL have not been described before and seem to be metformin-specific.

Adult

Low-dose oral contraceptives lower plasma levels of apolipoprotein E.

Three different oral contraceptive preparations were studied before and after a 3 month treatment period with respect to their effects on plasma lipoprotein parameters. A total of 58 healthy women requesting oral contraception were randomly assigned to three groups. Each woman received either monophasic preparations containing ethinylestradiol and desogestrel (M-DG); ethinylestradiol and gestodene (M-GD); or a triphasic preparation of ethinylestradiol and levonorgestrel (T-LN). As has been reported in other studies, the concentrations of total plasma cholesterol and apolipoproteins B and A-IV did not change significantly in any group. HDL cholesterol, triglycerides, apolipoproteins A-I and A-II increased or tended to increase. Despite the effects of the three hormone preparations on these lipoprotein parameters, however, each led to a highly significant decrease in apolipoprotein E plasma levels. Considering the recently reported observations that oral contraceptives increase the hepatic uptake of cholesterol-rich remnants, this decrease in apo-E plasma levels may in women that take oral contraceptives be directly correlated with increased hepatic lipoprotein metabolism.

Adolescent

Normolipemic dysbetalipoproteinemia and hyperlipoproteinemia type III in subjects homozygous for a rare genetic apolipoprotein E variant (apoE1).

A family with three heterozygote and two homozygote carriers of the rare apolipoprotein E1 isoform was detected by isoelectric focusing. One of the homozygous patients had type III hyperlipidemia, while the other showed normolipemic dysbetalipoproteinemia. Restriction fragment length analysis as well as allele specific oligonucleotides were used to identify the structural alterations forming the abnormal epsilon 1 genotype. Comparison with the most common epsilon 3 allele showed that two base exchanges A for G in codon 127 and T for G in codon 158 (Asp for Gly and Cys for Arg, respectively) are responsible for the amino acid substitution which causes the charge shift observed in isoelectric focusing. The same defects have been described in the only previously characterized apoE1 (Weisgraber et al. 1984. J. Clin. Invest. 73: 1024-1033). In addition to the study by Weisgraber and coworkers, who reported on a heterozygous patient, we here describe the metabolic and clinical consequences of a homozygosity for this rare allele. Changes in lipoprotein metabolism, as well as in clinical phenotypes, were exactly identical to those seen in patients homozygous for the epsilon 2 allele, which has in common with the epsilon 1 allele the mutation in codon 158, but lacks the substitution in codon 127. In addition, lipoprotein profiles of the epsilon 3/epsilon 1 heterozygotes were indistinguishable from those of epsilon 3/epsilon 2 heterozygotes. Therefore, we conclude that the additional mutation in codon 127 that characterizes the epsilon 1 allele is of no functional importance in vivo.

Adolescent

A rapid laser immunonephelometric assay for serum amyloid A (SAA) and its application to the diagnosis of kidney allograft rejection.

We set up a laser nephelometric assay for the quantitation of serum amyloid A (SAA) in human plasma. Therefore monospecific antibodies were raised in sheep and used in parallel to measure SAA concentrations by nephelometry and also by radial immunodiffusion, an assay usually applied for determination of SAA. The nephelometric method is precise, simple and unlike radial immunodiffusion results are obtained within an hour. The antigen concentrations determined both by laser nephelometry and radial immunodiffusion correlated highly (r = 0.98). As plasma SAA concentrations were reported to be a possible marker of kidney allograft rejection, the assay was applied to measure SAA concentrations in patients after kidney transplantation. Data were compared with clinical and other biochemical parameters. The period after kidney transplantation is reported for two cases, where SAA plasma concentrations were helpful in diagnosing allograft rejection. The rapid availability of the SAA plasma concentrations by nephelometry makes them a possible additional tool to decide quickly upon antirejection therapy.

Graft Rejection

Polymorphism of apolipoprotein E influences levels of serum apolipoproteins E and B in the human neonate.

To gain more insight into the genetic vs. environmental influence of the apoE phenotypes on plasma lipoprotein variation we studied human umbilical cord sera at birth. Apolipoprotein E genetic phenotypes were determined in 110 individuals by immunoblotting and shown to be identical to the adult human isoforms with six phenotypes present and occurring at a similar frequency as reported previously for the adult population in the same area. Total serum cholesterol and triglyceride levels were low in the neonates and did not differ significantly between apoE phenotypes. On the other hand as in the adult, levels of apoE and B differed significantly between the phenotypes. ApoE was highest in individuals with the epsilon 2 allele and lowest in individuals expressing apoE4, and vice versa for apoB. We conclude that apoE phenotypes in human umbilical cord blood serum are already associated with pronounced differences in apoE and B levels in the newborn. The study demonstrates that the association of apoE and apoB levels with the apoE polymorphism occurs independently of significant enteral nutrition in the relatively constant in utero environment.

Apolipoproteins B

Apolipoproteins in human amniotic fluid: concentrations, isoforms and polymorphism.

Apolipoproteins were determined in 50 human amniotic fluids obtained by amniocentesis during weeks 16 and 22 (n = 26) or 33 and 41 (n = 24) of gestation. Whereas apo A-I, A-II, A-IV, and E were identified at levels of 1, 0.7, 0.8 and 1% of normal human adult plasma, respectively, apo B levels were only 0.04% of plasma concentration and apo C-III levels were below the detection limits of the assay. Amniotic fluid levels of apo A-II, A-IV and E did not differ between early and late stages of pregnancy, but levels of apo B decreased and apo A-I increased significantly in late pregnancy. Isofocusing showed apo A-I, A-II and A-IV in identical positions as compared to human adult plasma. Furthermore the known genetic polymorphism of apo A-IV was detectable. Individuals heterozygous, for the variant form apo A-IV-2, showing the phenotype apo A-IV (2-1), had significantly higher levels of apo A-I and A-II as compared to the common phenotype apo A-IV (1-1). We conclude that human amniotic fluid contains the major plasma apolipoproteins at about 1% of plasma levels with the exception of apo B which shows a level at an order of magnitude less than high-density lipoprotein apoproteins in comparison to their plasma counterparts.

Amniotic Fluid

[Does determination of atrial natriuretic factor have significance in the assessment of cardiac stress in apnea in sleep apnea patients?].

It has long been known that the heart is involved volume regulation. This fact took on new importance when, in 1981, de Bold discovered the existence of ANF. Apnea-associated cardiovascular changes make the treatment of apnea necessary to prevent the occurrence of cardiovascular sequelae. What is needed, however, is a parameter which, non-invasively, reflects both the cardiac loading during apnea and effects of treatment. Krieger succeeded in demonstrating that the commonly observed nycturia regresses under nasal cPAP therapy. This prompted us to consider whether the ANF factor might not be involved. In an attempt to find an answer, we have, up to now, investigated six patients prior to and during nCPAP therapy. On the basis of the results we obtained, the following conclusions may be drawn: 1. During apnea, the patients show sometimes dramatic increases in ANF plasma levels. 2. Under nasal CPAP treatment, these elevated levels decrease again, in some cases by as much as 50%. 3. The ANF plasma level correlates with pulmonary arterial pressure. This suggests to us that ANF determination is of importance for the assessment of cardiac loading during apnea, and represents a parameter that reflects the effects of therapy.

Atrial Natriuretic Factor

[Hyperestrogenemia following various shunt operations: on the role of estrogens in the development of focal nodular hyperplasia of the liver].

Hormones especially estrogens have been suspected to induce liver cell tumours or hepatic focal nodular hyperplasia (FNH). In rats 6 months after portocaval anastomosis (PCA) the occurrence of FNH has been observed. Modified portocaval anastomosis (mPCA) does not lead to FNH. To test the concept of estrogen induced tumour formation we measured in both groups as well as in a shamoperated control group (SOP) the levels of estradiol (E2), estrone (E1) and of testosterone (T). In a further experiment the hormone levels were measured in rats with portocaval transposition (PCT), an operation which leads to high gonadal hormone production. In groups of 6 male rats each (280-300 g) either SOP, PCA, mPCA or PCT were performed. 30 days later the blood levels of E2, E1, and of T were measured by radioimmunoassay. In PCT-rats hormone levels were measured in the blood synchronously taken from the inferior vena cava (prehepatic) and from the heart (posthepatic), to get an information of the hepatic hormone degradation. After PCA the median level of E2 (77 pg/ml) and E1 (63 pg/ml) are significantly elevated when compared with SOP-rats (41 and 43 pg/ml). Equally after mPCA the E2 and E1 levels are significantly higher (61 and 70 pg/ml) than in controls rats. In contrast the concentrations of T are significantly reduced (PCA 0.03, mPCA 0, 10, SOP 1.0 ng/ml). PCA as well as mPCA result in a hyperestrogenic and hypoandrogenic status. When PCA and mPCA are compared, only the testosterone blood levels are significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals