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Biomedical subjects

G Baumann

Publications and source records attributed to G Baumann.

At least 145 records · Page 8Linked to original sources
PubMed1997

Temporary tracheobronchial stenting in malignant stenoses.

Endobronchial stent implantation has been successfully employed in malignant stenoses. The aim of this prospective study was to investigate the temporary use of tracheobronchial stents combined with tumour-specific therapy. All patients received stents for primary palliation of dyspnoea followed by radio- or chemotherapy with the aim of stent removal after reduction of the stenosis. In 22 patients suffering from severe malignant strictures, 34 endobronchial stents (29 Strecker-, 3 Dumon-, 1 Orlowski-, 1 Dynamic-Y-stents) were implanted (in 9 patients, 2 stents were necessary). Patients were treated by irradiation (n = 18) or chemotherapy (n = 4) after stent implantation. Significant improvement of dyspnoea (P < 0.001) and partial oxygen pressure (P < 0.01) was observed. In 11 out of 22 cases (50%), the stents could be removed after successful tumour-specific therapy which led to reduction of stenosis after a mean interval of 31.7 (6-104) days (temporary stenting). During the period of tumour-specific therapy, 9 patients died after a mean interval of 132 (13-347) days (definite stenting). In two cases, stents had to be removed after stent compression, stent dislocation and severe cough. The results suggest that temporary stenting, characterised by subsequent successful tumour-specific therapy, is a new valuable therapeutic strategy. It can "bridge the gap" before tumour-specific therapy can take effect. If tumour-specific therapy is ineffective, definite stenting is the palliative method of choice in severe dyspnoea in bronchial carcinoma.

Adult↗
PubMed1997

Surgical removal of atrial septal defect occlusion system-devices.

OBJECTIVE: Since 1976 a number of similar transvenous atrial septal defect occlusion systems have been developed and applied to prevent surgical intervention with extracorporeal circulation and the complications involved. One of them is the so called atrial septal defect occlusion system (ASDOS-device; Dr Ing Osypka, Germany). METHOD AND RESULTS: In our institution, eight ASDOS-devices were implanted in adults during the last year. In six individual cases, these devices were explanted because of thrombosis, residual shunts, deformations of the umbrella, disconnection of the system and atrial perforation with hemopericard. This occured 17-380 days after the implant. The surgical removal was uncomplicated in all cases. CONCLUSIONS: Because the complication rate of the ASDOS-device was unacceptably high, surgical repair was preferred.

Adult↗
PubMed1997

Arousals and sleep stages in patients with obstructive sleep apnoea syndrome: Changes under nCPAP treatment.

Nocturnal arousals are the essential cause of disturbed sleep structure in patients with obstructive sleep apnoea syndrome (OSAS). The aim of this study was to analyse the relationship between sleep stages, respiratory (type-R) and movement (type-M) related EEG arousals. Furthermore, the value of these arousals as a criterion for the efficiency of nCPAP treatment was estimated. We examined 38 male patients aged between 30 and 71 (49.1 +/- 20.9 SD) y. All patients suffered from OSAS. The mean respiratory disturbance index (RDI) was 47.3 +/- 27.8 per h. Polysomnographic monitoring was carried out on 4 subsequent nights: baseline night, 2 nights of nCPAP titration and nCPAP control night. Sleep was visually scored and EEG arousals were classified into type R and M, depending on whether changes of respiration or movement caused the arousal. The RDI, the R index (type-R/h), the M index (type-M/h) and the R and M indices in different sleep stages were calculated. During the baseline night a deficit of slow wave sleep (SWS) and REM sleep was found. Furthermore there were more type-R than type-M arousals registered (17.4 h-1 [3.6-43.6] vs. 5.9 h-1 [1.6-11.8]) (P < 0.01). They occurred during stages NREM 1, NREM 2 and REM (P < 0.01). An SWS sleep rebound and a reduction of the SWS and REM latencies were already found during the first CPAP night. The R index was reduced during the first CPAP night in all sleep stages (P < 0.01) and remained approximately the same in the following 2 nights (3. CPAP night: 1.1 h-1 [0.3-5.0]). Type M arousals occurred more in stages 1 and 2 (P < 0.01), and remained unchanged under nCPAP. We concluded that differentiation of nocturnal arousals may provide more detailed information regarding the influence of breathing disturbances on sleep. Respiratory related, not movement related, arousals may be a useful additional tool in judging the efficiency of OSAS.

Adult↗
PubMed1997

Relationship between haemodynamics and morphology in pulmonary hypertension. A quantitative intravascular ultrasound study.

BACKGROUND: Intravascular ultrasound imaging of the pulmonary arteries has been demonstrated to be a reliable method of quantifying vessel diameter, luminal area and pulsatility. Simultaneous measurement of flow velocity and its response to vasodilators allows the relationship between morphology and functional compromise to be studied, especially endothelial dysfunction. METHODS: In 51 patients (mean age = 49.8 +/- 12.6 years, 17 female) we performed right heart catheterization and simultaneous intravascular ultrasound of pulmonary artery branches. The patients were divided in two groups: group 1 with normal pulmonary artery pressure and pulmonary vascular resistance, and group 2 with pulmonary hypertension (peak pulmonary artery pressure > 30 mmHg and/or mean pulmonary artery pressure > 20 mmHg). Vessel wall and lumen were studied using a 2.9 F intravascular ultrasound catheter with a 30 MHz phased array transducer. Measurement of blood flow velocity was accomplished by a Doppler flow wire (0.018 inch). The maximal flow change during acetylcholine infusion (adjusted to 10(-6); 10(-5), and 10(-4) M concentration in the blood vessel) was measured. RESULTS: There were no significant differences between groups 1 and 2 with respect to age (48.5 +/- 14.3 years vs 50.3 +/- 12.3 years; P = ns), gender (4 female/8 male vs 13 female/26 male; P = ns), luminal area of the vessel segment in which the intravascular ultrasound measurements were obtained (11.8 +/- 6.1 mm2 vs 16.7 +/- 14.3 mm2; P = ns), internal diameter (3.9 +/- 1.2 mm vs 4.2 +/- 1.7 mm; P = ns), and external diameter (6.1 +/- 1.3 mm vs 6.9 +/- 2.1 mm; P = ns). Cross-sectional images of the pulmonary artery wall demonstrated a single ring with high echodensity with a thin inner layer regarded as intima in group 1. In contrast, the majority of patients (n = 35/39) in group 2 demonstrated a thickening of the intimal layer and/or a disturbance of layering of the echogenic arterial wall. The relative wall thickness was higher in group 2 than in group 1 (22.5 +/- 10.4% vs 15.3 +/- 6.5%; P < 0.05). There were no significant correlations between pulmonary artery pressure and wall thickness pulmonary artery pressure and area change in the cardiac cycle, acetylcholine-dependent increase in pulmonary flow and morphological changes in the vessel wall. CONCLUSION: We conclude that intravascular ultrasound is capable of detecting morphological changes in the pulmonary vessel wall in pulmonary hypertension and that vessel wall hypertrophy of small pulmonary segment arteries, as detected by intravascular ultrasound, is not predictive of functional vasodilatory response of resistance vessels of the same vessel area.

Aged↗
PubMed1997

Respiratory muscle weakness and normal ventilatory drive in dilative cardiomyopathy.

BACKGROUND: In dilative cardiomyopathy several factors influence dyspnoea. Patients with chronic heart failure may demonstrate impairment of breathing pattern, ventilatory drive and respiratory muscle strength, as well as reduction of ventilatory efficiency. The purpose of this study was to evaluate whether dilative cardiomyopathy is accompanied by changes in breathing pattern, respiratory muscle weakness and ventilatory neural drive. METHODS: We investigated 47 patients (36 men, mean age = 47.8 +/- 11.2 years) with chronic heart failure due to dilative cardiomyopathy, and 30 healthy subjects (10 men, mean age = 35.4 +/- 11.7 years) served as controls. Patients and controls underwent evaluation of left ventricular ejection fraction by 2D echocardiography, spirometry, body plethysmography, mouth occlusion pressure and respiratory muscle strength, as well as by submaximal treadmill exercise testing with gas exchange measurements. The patients' results were compared to controls and predicted standard normal values, and evaluated for differences according to the degree of severity of functional impairment. RESULTS: Patients with dilative cardiomyopathy demonstrated a slight reduction in lung volumes (15% of the patients with obstructive and 15% with restrictive lung function pattern) and diffusion capacity (20.4 +/- 6.8 vs 15.4 +/- 6.7 ml.min-1.kPa-1; P < 0.01). In neural drive, as assessed by mouth occlusion pressure, there was no significant difference between patients and controls. There was a slight but significant reduction in respiratory muscle strength, as assessed by measuring maximal inspiratory pressure in patients with dilative cardiomyopathy (6.7 +/- 2.4 kPa vs 8.6 +/- 3.5 kPa; P < 0.01). The observed changes were more pronounced in the severe chronic heart failure patients (with a reduction in ventilatory efficiency) whereas no relationship among indices of cardiac or respiratory function was found. CONCLUSIONS: Patients with chronic heart failure due to dilative cardiomyopathy develop respiratory muscle weakness without changes in neural ventilatory drive, and slight changes in breathing pattern related to the severity of the disease.

Adult↗
PubMed1997

Role of growth hormone status in the outcome of total knee replacement.

The objective was to assess whether the aging related, variable decline in growth hormone influences total knee replacement outcome. In this prospective cohort study, consecutive patients who underwent unilateral total knee replacement and who met criteria were enrolled from the practice of 1 orthopaedic surgeon at a university hospital. Participants were evaluated 1 month before and 3 months after total knee replacement. Evaluators were not involved in patient care. The primary outcome measure was the Medical Outcome Study 36-item Short Form Health Survey Physical Functioning Scale score 3 months after total knee replacement. In a multiple regression analysis performed to assess the influence of growth hormone status, controlling for social support, body mass index, gender, previous reconstruction, mental health, motivation, and baseline physical functioning, only mental health contributed significantly to outcome. Mental health accounted for 18% of outcome variance. Growth hormone levels did not predict functional status after total knee replacement. Psychological status contributes significantly to total knee replacement physical functional outcome.

Age Factors↗
PubMed1997

The Dwarfs of Sindh: severe growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene.

We report the discovery of a cluster of severe familial dwarfism in two villages in the Province of Sindh in Pakistan. Dwarfism is proportionate and occurs in members of a kindred with a high degree of consanguinity. Only the last generation is affected, with the oldest dwarf being 28 years old. The mode of inheritance is autosomal recessive. Phenotype analysis and endocrine testing revealed isolated growth hormone deficiency (GHD) as the reason for growth failure. Linkage analysis for the loci of several candidate genes yielded a high lod score for the growth hormone-releasing hormone receptor (GHRH-R) locus on chromosome 7. Amplification and sequencing of the GHRH-R gene in affected subjects demonstrated an amber nonsense mutation (GAG-->TAG; Glu50-->Stop) in exon 3. The mutation, in its homozygous form, segregated 100% with the dwarf phenotype. It predicts a truncation of the GHRH-R in its extracellular domain, which is likely to result in a severely disabled or non-existent receptor protein. Subjects who are heterozygous for the mutation show mild biochemical abnormalities in the growth hormone-releasing hormone (GHRH)--growth hormone--insulin-like growth factor axis, but have only minimal or no growth retardation. The occurrence of an offspring of two dwarfed parents indicates that the GHRH-R is not necessary for fertility in either sex. We conclude that Sindh dwarfism is caused by an inactivating mutation in the GHRH-R gene, resulting in the inability to transmit a GHRH signal and consequent severe isolated GHD.

Adolescent↗
PubMed1997

Regulation of tumor necrosis factor alpha- and interleukin-1-beta-induced induced adhesion molecule expression in human vascular smooth muscle cells by cAMP.

This study investigates the hypothesis that the elevation of intracellular cAMP may affect cytokine-induced expression of adhesion molecules on human vascular smooth muscle cells. In cultured human smooth muscle cells from coronary arteries and saphenous veins, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) induced the expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1), whereas interferon-gamma (INF-gamma) selectively stimulated the expression of ICAM-1. Adenylyl cyclase was stimulated either by the stable prostacyclin mimetic cicaprost or by forskolin. Adhesion molecules were detected by a cell surface enzyme immunoassay and the respective mRNA by reverse transcriptase polymerase chain reaction (rt-PCR). Cicaprost as well as forskolin significantly inhibited TNF-alpha- and IL-1 beta-induced cell surface expression of ICAM-1 and VCAM-1. Semiquantitative rt-PCR measurements showed a marked decrease of TNF-alpha- and IL-1 beta-induced mRNA levels of both adhesion molecules after preincubation with cicaprost. The stability of TNF-alpha-induced ICAM-1 and VCAM-1 expression at mRNA and protein level was not altered by cicaprost. The IFN-gamma-induced increase of cell surface expression of ICAM-1 and the respective mRNA levels, however, were not significantly altered by elevation of intracellular cAMP. Basal and stimulated cAMP levels, measured by radioimmunoassay, did not differ in TNF-alpha- and IFN gamma-treated cells. The present results demonstrate that the expression of adhesion molecules on human smooth muscle cells induced by cytokines is differentially modulated by activation of adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗
PubMed1997

A kindred with a variant of multiple endocrine neoplasia type 1 demonstrating frequent expression of pituitary tumors but not linked to the multiple endocrine neoplasia type 1 locus at chromosome region 11q13.

Acromegaly is uncommon in kindreds with multiple endocrine neoplasia type 1 (MEN1), whereas primary hyperparathyroidism (PHP) has the highest penetrance of any endocrinopathy. We report an unusual MEN1 kindred with frequent expression of pituitary tumors and a low penetrance of PHP. Four members were found to have disease: PHP in generation I, acromegaly (2 cases) in generation II, and hyperprolactinemia associated with a pituitary tumor in generation III. There was no evidence for PHP in 1 patient with acromegaly (age 60 yr), the patient with hyperprolactinemia and the pituitary tumor (age 22 yr), and 1 asymptomatic obligate carrier (age 50 yr). Screening of 26 members revealed the possible diagnosis of PHP in 1 family member in generation II and possible early acromegaly in 2 members of generation III with elevated serum concentrations of insulin-like growth factor I and insulin-like growth factor-binding protein-3 but normal patterns of pulsatile GH release. Although the predisposing genetic defect in typical MEN1 families has previously been mapped to chromosome location 11q13 without evidence of heterogeneity among the 87 families analyzed, linkage of disease in this family to the MEN1 region is unlikely based on haplotype analysis. Localization of the gene(s) responsible for disease in such atypical families may aid in the understanding of the pathogenesis of MEN1. In addition, further study of the earliest changes in patterns of pulsatile GH release in familial acromegaly may allow more insight into the pathogenesis and natural history of this disease.

Acromegaly↗
PubMed1997

Deletion of the mouse GH-binding protein (mGHBP) mRNA polyadenylation and splicing sites does not abolish production of mGHBP.

In murine species, the GH receptor (mGHR) gene encodes a full-length membrane-anchored mGHR and a truncated soluble receptor ectodomain (the GH-binding protein; mGHBP). The mGHR and mGHBP mRNAs are generated by alternative pre-mRNA splicing. Similar GHR/GHBP pairs are generated in other species by proteolysis of the GHR. The regulation of GHBP expression and the biological role of GHBP are not clear. In order to begin to dissect the factors responsible for regulating expression of mGHR and mGHBP, we have cloned a mouse GH receptor/binding protein (mGHR/BP) minigene consisting of two mGHR cDNA fragments and an mGHR/BP genomic sequence, such that the mGHR and mGHBP can be derived from the minigene by mimicking native alternative pre-mRNA splicing. To study the possible role of selection of polyadenylation relative to the expression of mGHR and mGHBP, we deleted the two tandem poly A addition signals and the flanking AT-rich region within the exon (exon 8A) that encodes the carboxy terminus of mGHBP. In addition, two other mutated forms of the minigene, one containing a mutated alternative splice acceptor site (SAS) near exon 8A and the other possessing a deletion of the intron between exons 7 and 8A (intron 7/8A), were generated. Expression of the mGHR/BP minigene and its mutated forms in transfected mouse L cells revealed that removal of the polyadenylation signals diminished but did not abolish either mGHR or mGHBP production. However, mutation of the SAS yielded normal mGHR and an mGHBP which may be a result of the translation of an mRNA possessing an open reading frame in intron 7/8A. Additionally, removal of intron 7/8A abolished mGHR expression but resulted in mGHBP production. The results suggest that selection of alternative polyadenylation sites of the mGHR/BP gene does not play a major role in the regulation of expression of mGHR and mGHBP in vitro. These results also suggest that mutation of the SAS near exon 8A does not abolish the ability of mGHR/BP gene to produce an mGHBP that retains the ability to bind GH, although the new mGHBP may be different from the natural mGHBP at its carboxy terminus.

Amino Acid Sequence↗
PubMed1997

Severe prosthetic valve-related endocarditis following dental scaling: a case report.

There is a well-known correlation between surgical dental procedures and the risk of bacterial endocarditis in patients with prosthetic cardiac valves. A 43-year-old patient with prosthetic aortic and mitral valves, which already have been removed twice because of endocarditis, suffered from a prosthetic valve-related endocarditis following dental scaling, which was performed without any antibiotic prophylaxis. Invasive medical procedures in patients with prosthetic heart valves may lead to endocarditis. Antibiotic prophylaxis is recommended even for dental procedures considered to be "harmless," such as dental scaling.

Adult↗
PubMed1997

[Multiple sleep latency test in patients with obstructive snoring].

The objective of our study was to examine the effect of the n-CPAP on day tiredness of patients suffering from obstructive snoring. This effect was objectified by means of the Multiple Sleep Latency Test (MSLT). The MSLT was performed with optimal pressure at 8.00, 10.00, 12.00 and 14.00 hrs. subsequent to the control night and the third CPAP night. The latencies of falling asleep and the sleep stages were determined in accordance with the criteria of Rechtschaffen and Kales. The average latency of falling asleep before therapy was: at 8.00 hrs 9.0 +/- 14.2 min, at 14.00 hrs. 7.2 +/- 6.3 min. The following latencies of falling asleep were observed after the third CPAP night: 8.00 hrs. 14.2 +/- 6.3, 10.00 hrs. 13.4 +/- 6.4, 12.00 hrs. 13.7 +/- 6.4 hrs. 13.7 +/- 6.0 min. This means that after the therapy there was a marked tendency to longer latencies at all 4 points of measurement with significant differences at 12.00 and 14.00 hrs. A comparison of the quality of sleep before and after the therapy yielded an increase in deep sleep and a significant increase in REM density during dream sleep. MSLT enabled objectivation of improved sleep quality and of subjective decrease in day tiredness after CPAP therapy in patients with obstructive snoring. The latency in falling asleep increased at all the points of measurement. Nevertheless, interindividual differences are great, compared with the uniform subjective success of CPAP therapy achieved with these patients.

Adult↗
PubMed1996

Catalytic specificity of phosphotyrosine kinases Blk, Lyn, c-Src and Syk as assessed by phage display.

Protein tyrosine kinases (PTKs) are implicated in cell proliferation, differentiation, and receptor-mediated signalling events. Recruitment of intracellular PTKs into the signalling complex, often localized at the inner surface of the cell membrane, involves SH2 and SH3 domains attached to the catalytic kinase domain. While the interaction of SH2 and SH3 domains with their target sequences is well documented in a number of cases, the contribution of the catalytic domain itself in conferring specificity to a given signal cascade is not fully understood. We addressed this question and employed the phage display technique to assess the substrate requirements for the highly related Src-like PTKs c-Src, Blk, Lyn and the distantly related Syk. A diverse peptide library on phage was established, and after multiple rounds of phosphorylation and selection of phage displaying phosphotyrosine-containing peptides, canonical substrate sequences for each of the PTKs were enriched. The PTKs Blk and Lyn implicated in B cell signalling were found to prefer peptide substrates of the structure I/L-Y-D/E-X-L which resemble critical features of the ITAM motifs found in, e.g. the intracellular components Ig-alpha and Ig-beta of the beta cell receptor. All Src-like PTKs had a requirement for isoleucine or leucine in the position -1 with respect to the phosphorylated tyrosine residue in position 0. While Blk and Lyn had a strong preference for a negatively charged amino acid in position +1, c-Src preferred tryptophan or glycine in this position. Syk, not belonging to the Src-like PTK family, revealed a distinct substrate requirement for aspartic acid in position -1 and glutamic acid in position +1. In general, all PTKs we have tested had a strong preference for a particular amino acid in the positions -1 and +1 adjacent to the tyrosine residue.

Amino Acid Sequence↗
PubMed1996

Fractals for multicyclic synthesis conditions of biopolymers. Examples of oligonucleotide synthesis measured by high-performance capillary electrophoresis and ion-exchange high-performance liquid chromatography.

We have developed models of patterns for nucleotide chain growth. These patterns are measurable by high-performance capillary electrophoresis and ion-exchange high-performance liquid chromatography in crude products of solid-phase synthesized 30mer and 65mer oligodeoxyribonucleotide target sequences N. We introduce mathematical methods for finding characteristic values d(o) and p(o) for constant chemical modes of growth as well as d and p for non-constant chemical modes of growth (d = probability of propagation, p = probability of termination). These methods are employed by presenting the accompanying computer software developed by us in C code, Mathematica R languages, and Fortran. Characteristic values of the parameters d, p, and the target nucleotide length N describe the complete composition of the crude product. From this we have developed the relation 2 - [N/(N - 1)]/Da, measurable(N,d) as a universal quantitative measure for multicyclic synthesis conditions (D, fractal dimension and similarity exponent, respectively). We use this mathematical treatment to compare the efficiency of oligodeoxyribonucleotide syntheses of different target length N on polymer support materials. Further, we analyze selected syntheses of short and long oligodeoxyribonucleotides as well as single-stranded DNA sequences by well-known empirical autocorrelation, fast Fourier transformation, and embedding dimension techniques.

Base Sequence↗
PubMed1996

Rapid identification of phosphopeptide ligands for SH2 domains. Screening of peptide libraries by fluorescence-activated bead sorting.

A method for the identification of high-affinity ligands to SH2 domains by fluorescence-activated bead sorting (FABS) was established. Recombinant SH2 domains, expressed as glutathione S-transferase (GST) fusion proteins, were incubated with a phosphotyrosine (Y*)-containing peptide library. 6.4 x 10(5) individual peptides of nine amino acids in length (EPX6Y*X19X7X19X7X6) were each displayed on beads. Phosphopeptide interaction of a given SH2 domain was monitored by binding of fluorescein isothiocyanate-labeled antibodies directed against GST. High-fluorescence beads were isolated by flow cytometric sorting. Subsequent pool sequencing of the selected beads revealed a distinct pattern of phosphotyrosine-containing motifs for each individual SH2 domain: the SH2 domain of the adapter protein Grb2 predominantly selected beads with the sequence Y*ENDP, whereas the C-terminal SH2 domain of the tyrosine kinase Syk selected Y*EELD, each motif representing the most frequently found residues C-terminal to the phosphotyrosine. For deconvolution studies, soluble phosphopeptides comprising variations of the Grb2 motifs were resynthesized and analyzed by surface plasmon resonance.

Amino Acid Sequence↗
PubMed1996

DNA polymorphisms in adhesion molecule genes--a new risk factor for early atherosclerosis.

To contribute to the analysis of the genetic background of atherosclerosis, especially endothelial dysfunction, we searched for DNA polymorphisms in the genes encoding E-, P-, and L-selectin, and ICAM-I and VCAM-I. We detected 17 mutations by single-strand conformation polymorphisms analysis and direct sequencing. Five of them resulted in an amino acid substitution. In E-selectin, exchanges from serine to arginine (position 128), from leucine to phenylalanine (position 554), and a DNA mutation from guanine to thymine (position 98) present significantly different allele frequencies in young patients with angiographically established, severe atherosclerosis, compared with an unselected population. Results suggest that these polymorphisms are associated with a higher risk for early severe atherosclerosis.

Adult↗
PubMed1996

Growth hormone binding protein and free growth hormone in chronic renal failure.

Chronic renal failure in children is associated with growth failure. While the pathogenesis of uremic growth failure is multifactorial, an abnormal growth hormone/ insulin-like growth factor (GH-IGF) axis is an important contributory element. Patients with uremia exhibit insensitivity to the action of GH, as exemplified by high plasma GH levels, low IGF-I activity, and poor somatic growth. This insensitivity can be overcome by supraphysiological doses of exogenous GH. Plasma GH binding protein (GHBP, the circulating ectodomain of the GH receptor) levels are decreased in patients with renal failure, as are hepatic GH receptor levels in animal models. Since GHBP levels are thought to reflect GH receptor levels in tissues, it is likely that the uremic GH insensitivity in humans is mediated by a decreased number of GH receptors. Another implication of the low plasma GHBP is a disproportionate elevation of free plasma GH (the biologically active moiety) relative to total GH, lending additional support to the concept of GH insensitivity in uremia. GH kinetics are altered in renal failure because of: (1) inability to excrete GH and (2) changes in the bound fraction of GH in the circulation.

Child↗