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Biomedical subjects

M G Mohaupt

Publications and source records attributed to M G Mohaupt.

18 recordsLinked to original sources

[Urinary hormone analysis].

Urinary hormone analysis is applied to detect an altered steroid hormone metabolism, an elevated production of biogenic amines and to non-invasively determine the protein hormone human beta-choriogonadotropin indicating a pregnancy. Occasionally, these determinations need to be complemented by plasma- or serum hormone analysis. Clinical data including current drug therapy and urinary creatinine as reference are required to interpret any urine analysis. Diseases to be investigated by steroid hormone analysis are excess production of a typical or atypical mineralocorticoid active steroid hormones, the hormonal activity of adrenal or ovarian tumors, acne of unknown origin, hirsutism, a PCO-, an adrenogenital or a suspected Cushing syndrome. Biogenic amines should be determined in suspected secondary or refractory arterial hypertension, in case of pheochromocytoma- or paraganglioma-associated symptoms or if a serotonin-producing tumor is suspected. In children genetically determined diseases are the primary background to perform an analysis.

Endocrine System Diseases↗

Intermediate outcome and risk factor assessment of bovine vascular heterografts used as AV-fistulas for hemodialysis access.

OBJECTIVES: This observational study was set up to prospectively follow all bovine heterograft (ProCol) fistulas implanted for hemodialysis access between 1998 and 2002. METHODS: ProCol was implanted if autogenous vein was not available or if patients presented with a history of failed, infected or otherwise complicated ePTFE grafts and/or on immunosuppressive therapy. Fistula patency was the primary outcome; secondary outcomes were clinical events and the rate of access revisions. RESULTS: Sixty-two ProCol grafts were implanted in 56 patients. The mean primary (PP) and secondary patency (SP) was 334 (SEM 57) and 528 (SEM 59) days, respectively. Coronary heart disease was associated with a significantly better SP (OR 0.2, 95% CI 0.1-0.9) whilst diabetes mellitus was associated with a significantly worse SP (OR 0.2, 95% CI 0.1-0.9). Reinterventions were performed at a mean rate of 1.23 (SEM 0.17) per fistula. The relative risk of access revision was significantly higher in patients with diabetes mellitus (OR 9.2, 95% CI 2.3-37.2). CONCLUSIONS: ProCol grafts, used for AV-fistulas, demonstrate acceptable patency rates in high-risk haemodialysis patients. Diabetes mellitus jeopardizes the patency of these fistulas and is associated with a high revision rate.

Animals↗

[Edema in pregnancy--trivial?].

In pregnancy total body water increases. At least 25% of the fluid will be distributed to the interstitial space, ultimately clinically imposing as lower leg edema of pregnant women. Next to a cumulative sodium retention, altered local Starling forces and changes in the hydration of extracellular matrix add to the fluid shift. Edema have to be expected in most of the pregnant women and should not be used to diagnose preeclampsia. Atypical edema localization and local, unilateral edema should cast suspicion of other dangerous complications of pregnancy. Diuretics should be restricted to pulmonary edema of preeclampsia, but these drugs are not to be used to manage edema of pregnancy.

Body Weight↗

Delay of dialysis in end-stage renal failure: prospective study on percutaneous renal artery interventions.

BACKGROUND: Renal artery stenosis (RAS) is a cause of end-stage renal failure. We studied the effect of percutaneous renal artery intervention (PRI) in patients with advanced, progressive disease at risk for renal failure, hypothesizing a beneficial effect. METHODS: Thirty-nine primary and 14 secondary PRIs were performed on 28 patients with atherosclerotic RAS, serum creatinine >300 micromol/L, and progressive loss of renal function >/=1 year before PRI. Renal function and RA patency were prospectively followed for 12 months after primary and secondary PRI. The intervention's effect on the progressive loss of renal function was calculated by comparing reciprocal slopes of serum creatinine against time before and after PRI. RESULTS: Progression of renal failure slowed significantly following PRI. Mean (+/-SE) slopes of reciprocal serum creatinine values were: 6.69 +/- 0.97 L micromol(-1) day(-1) (x10(-6)) before and 6.76 +/- 3.03 L micromol(-1) day(-1) (x10(-6)) after PRI (P= 0.0007). Fifteen patients (53.5%) showed improvement or stabilization of progressive renal dysfunction. Out of 11 patients expected to become dialysis dependent within one year, 8 (72.7%) experienced an improvement in renal function sufficient to remain dialysis-free. Favorable outcome correlated with a lower creatinine level (P= 0.0137) and a more negative slope of progression (r= 0.49, P= 0.020) at entry. Mortality was 10.7%, and rate of local complications was 7.1%. Deterioration of renal function following PRI was suspected in 17.9% of patients. CONCLUSION: PRI may improve renal function and ultimately delay dialysis in patients with advanced renal failure. Possible advantages must be weighed against the risk of renal failure advancement and high procedure-related complication rate.

Aged↗

[Rhabdomyolysis].

Rhabdomyolysis is a severe clinical symptom of variable etiology. Acquired factors of exogenous origin such as traumata and endogenous metabolic disturbances have to be separated from hereditary disease as causative mechanism. Most frequently, exertional stress during hyperthermia, traumatic damage or ethanol abuse are observed. Almost independent of the diverse initial events, the pathogenesis follows a common final pathway with intracellular calcium accumulation and ATP depletion. Clinical symptoms vary. Seldom, the classical triad of muscle pain, weakness, and dark urine is observed. Recurrent episodes should raise suspicion of an inherited disorder. Severe complications are hypovolemia, electrolyte disorders with hyperkalemia and hypocalcemia resulting in life threatening arrhythmias, a compartment syndrome, disseminated intravascular coagulation and acute renal failure, which is frequently oligo-anuric. In combination with often severe underlying disease, renal failure causes death in 1/5 of the patients. The diagnosis is made with the determination of serum creatine kinase and the myoglobin levels in plasma and urine. Therapeutic options are to correct the hypovolemia with sufficient fluid supply, the prevention of oliguria using loop diuretics, alkalinization of the urine, normalization of serum electrolytes with reduction of hyperkaemia, and decompression of compartment syndromes. An underlying disease should be evaluated to initiate specific therapeutical and preventative steps. Avoiding pre-disposing factors by identifying the mechanisms of disease will reduce the occurrence of rhabdomyolysis with its still high mortality.

Acute Kidney Injury↗

Sirolimus-associated eyelid edema in kidney transplant recipients.

BACKGROUND: The immunosuppressant sirolimus is effective in preventing acute rejection episodes. So far, unusual edema formation has not been reported as a side effect. METHODS: Two groups of patients with renal transplants, consisting of 11 patients each, were followed for up to 29 months. The immunosuppressive regimen was either sirolimus and prednisone with or without cyclosporine or azathioprine/mycophenolate and prednisone with cyclosporine. Routine follow-up included a thorough clinical investigation. Edema formation was documented photographically. RESULTS: In 5 of the 11 patients treated with sirolimus uni- or bilateral, non-itching, eyelid edema was observed. After discontinuation of sirolimus, lid edema disappeared. The duration until recovery varied from weeks to months. No cause of edema formation other than the treatment with sirolimus was detected. CONCLUSIONS: Severe eyelid edema formation seems to be associated with sirolimus treatment. The underlying mechanism is unknown.

Adolescent↗

[Microhematuria--what next?].

Asymptomatic microhematuria is a common reason for a urological consultation. Uncertainty prevails as to how meticulous the work-up must be, to not miss relevant or even life-threatening underlying diseases. To date, the Urological Associations have not released any guidelines to which extent patients need to be examined for asymptomatic microhematuria, which therefore is managed individually by each urologist. There are various potential examinations that can be applied, ranging from a clinical examination to a kidney biopsy. After reviewing the literature, an algorithm has been developed, which should assure diagnosis of serious disease and at the same time avoid costly, unpleasant and unnecessary examinations.

Adult↗

3D Ultrasound imaging--a useful non-invasive tool to detect AV fistulas in transplanted kidneys.

BACKGROUND: A precise, non-invasive, non-toxic, repeatable, convenient and inexpensive follow-up of renal transplants, especially following biopsies, is in the interest of nephrologists. Formerly, the rate of biopsies leading to AV fistulas had been underestimated. Imaging procedures suited to a detailed judgement of these vascular malformations are to be assessed. METHODS: Three-dimensional (3D) reconstruction techniques of ultrasound flow-directed and non-flow-directed energy mode pictures were compared with a standard procedure, gadolinium-enhanced nuclear magnetic resonance imaging angiography (MRA) using the phase contrast technique. RESULTS: Using B-mode and conventional duplex information, AV fistulas were localized in the upper pole of the kidney transplant of the index patient. The 3D reconstruction provided information about the exact localization and orientation of the fistula in relation to other vascular structures, and the flow along the fistula. The MRA provided localization and orientation information, but less functional information. Flow-directed and non-flow-directed energy mode pictures could be reconstructed to provide 3D information about vascular malformations in transplanted kidneys. CONCLUSION: In transplanted kidneys, 3D-ultrasound angiography may be equally as effective as MRA in localizing and identifying AV malformations. Advantages of the ultrasound method are that it is cheaper, non-toxic, non-invasive, more widely availability and that it even provides more functional information. Future prospective studies will be necessary to evaluate the two techniques further.

Adult↗

Nitric oxide synthase activity and Doppler parameters in the fetoplacental and uteroplacental circulation in preeclampsia.

OBJECTIVE: We investigated the hypothesis that changes in blood flow in the uteroplacental and fetoplacental circulation in preeclampsia are associated with an abnormality of placental or uterine placental bed nitric oxide (NO) synthesis. METHODS: We measured pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries in 20 patients with preeclampsia and 14 healthy pregnant controls before elective cesarean section. During cesarean section, biopsies from the uterine placental bed and the placenta were taken and the nitric oxide synthase (NOS) activity was measured by the [3H] L-arginine-[3H] L-citrulline conversion assay in these samples. RESULTS: The NOS activity was significantly lower in the uterine placental bed in comparison to the placental tissue (p < 0.01). Placental NOS activity was similar between patients with preeclampsia and healthy controls and in the groups with either a pathological or a normal Doppler flow in the umbilical artery. In the uterine placental bed however, NOS activity from patients with preeclampsia was significantly lower (p < 0.01), whereas the blood flow resistance in the uterine arteries was elevated (p < 0.01) in comparison to healthy controls. CONCLUSIONS: Our data show that pathological Doppler waveforms in the uterine arteries of patients with preeclampsia are paralleled by diminished NOS activity in the uterine placental bed. Therefore, the compromised NO production in the uterine placental bed may play an important role in the impaired uteroplacental blood flow and potentially in some pathological features of preeclampsia such as intervillous thrombosis formation and fetal growth retardation.

Adult↗

Activation of purinergic P2Y2 receptors inhibits inducible NO synthase in cultured rat mesangial cells.

Cytokine-induced nitric oxide (NO) is produced on glomerular inflammation. Glomerular injury and thrombocyte aggregation result in the release of nucleotides, which may regulate induced NO synthesis in cultured rat mesangial cells (MCs). ATP (10(-3) M) inhibited 24-h nitrite production induced by lipopolysaccharide (LPS, 10 microg/ml)/interferon-gamma (IFN-gamma, 100 U/ml) by 48.2 +/- 6. 3%, as well as induction of inducible NOS (iNOS) protein and mRNA. Also, coincubation with either 10(-4) M of UTP, ATP, or ATPgammaS inhibited LPS/IFN-gamma-induced nitrite production by 29.9 +/- 5.8, 36.4 +/- 4.3, and 50.3 +/- 6.5%, respectively, indicating involvement of purinergic P2Y2 receptors. Correspondingly, cultured MCs expressed P2Y2 receptor mRNA. Agonists for other purinergic receptors [alpha,beta-methylene-ATP, 3'-O-(4-benzoyl)-benzoyl-ATP, 2-methylthio-ATP, ADP, UDP, adenosine] were ineffective. Treatment with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 10(-8) M) reproduced the inhibitory effect of ATP on iNOS protein expression and nitrite inhibition (by 46.6 +/- 10. 4%). The effect of ATP or PMA was reversed by the PKC inhibitors Ro-31-8220 (10(-8) M) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (10(-5) M), indicating that suppression of iNOS is mediated via activation of PKC through stimulated P2Y2 receptors. In conclusion, the release of purine mediators may play a critical role for iNOS expression and synthesis of NO during glomerular inflammatory disorders.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Anuria after delivery].

During the last decade certain peripartal complications decreased dramatically in industrialized countries. Here, a case of a 27 years old Caucasian primagravida will be presented. In the presence of symptoms of a severe preeclamptic condition with signs of an impending HELP syndrome the patient underwent Caesarean section. Within hours following surgery she developed complete anuria. Nuclear magnetic resonance imaging and histological evaluation of a renal biopsy led to the diagnosis of an acute, bilateral renal cortical necrosis. Besides the preeclamptic condition no further underlying disease was present, in particular no hemolytic-uremic syndrome. Following progress made in modern perinatal management renal cortical necrosis almost disappeared. Yet, in the presence of this disease a significant maternal morbidity and mortality still remains.

Adult↗

Endothelin-1 inhibits cytokine-stimulated transcription of inducible nitric oxide synthase in glomerular mesangial cells.

Endothelin-1 (ET-1) is a potent vasoconstrictor while nitric oxide (NO) has strong vasodilatory effects. Recent studies have indicated that vasoconstrictors and NO may mutually modulate their production and/or activity, thus regulating each other in the context of microcirculatory maintenance. We examined the question whether ET-1 may affect NO formation by controlling the expression of the inducible isoform of the NO synthase (iNOS) in cultured rat glomerular mesangial cells (MCs), as induced by the inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) plus interleukin-1 beta (IL-1 beta). We found that ET-1 in MCs markedly reduced cytokine-induced NO production (measured as stable NO2-) and inhibited the expression of iNOS mRNA (Northern blot analysis) and of iNOS protein (Western blotting). Inhibition of cytokine-stimulated iNOS mRNA expression by ET-1 was almost complete at the level of gene transcription while post-transcriptional effects were not detected. The ETA receptor antagonist BQ-123 blocked the inhibitory effect of ET1. The ETA agonist sarafotoxin 6b (S6b) inhibited, while the ETB agonist-sarafotoxin 6c (S6c) did not inhibit cytokine-initiated iNOS transcription in MCs. The results demonstrate that ET-1 can strongly inhibit cytokine induction of iNOS and formation of NO in cultured MCs, and that this action is mediated via the ETA receptor. While the precise mechanism(s) and biological relevance of this ET-1 effect are presently unclear, it is conceivable that down-regulation of iNOS by the vasopressor ET-1 may serve in vivo to prevent massive NO build-up and subsequent vasomotor collapse in the glomerular capillary tuft. This could help to maintain glomerular ultrafiltration in states of endotoxin excess as well as during glomerular formation and action of TNF-alpha and IL-1 beta causing iNOS induction and subsequent overproduction of NO.

Analysis of Variance↗

Cytokines activate inducible nitric oxide synthase gene transcription in inner medullary collecting duct cells.

The effects of lipopolysaccharide (LPS) and/or inflammatory cytokines on the expression of inducible nitric oxide synthase (iNOS) were studied in mIMCD-3 cells, derived from the murine inner medullary collecting duct. Under basal conditions, the production of nitrite, a stable metabolite of NO, was negligible; however, incubation with tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IF-gamma) for 24 h resulted in a 12-fold increase in nitrite synthesis and the appearance of abundant iNOS mRNA and protein. The induction of nitrite production and iNOS mRNA was time dependent, requiring approximately 8 h for expression of significant levels of nitrite or iNOS mRNA. Coincubation with the transcription inhibitor actinomycin D or the translation inhibitor cycloheximide prevented the cytokine induction of iNOS mRNA and NO production, indicating that synthesis of intermediary proteins stimulated transcription of the iNOS gene. Nuclear run-on transcription demonstrated that the iNOS gene was transcriptionally inactive under basal conditions, but was markedly induced by TNF-alpha and IF-gamma. These results indicate that inflammatory cytokines stimulate NO production in mIMCD-3 cells by activating iNOS gene transcription in a process that requires new protein synthesis.

Amino Acid Oxidoreductases↗

Role of NF-kappa B in the regulation of inducible nitric oxide synthase in an MTAL cell line.

The effects of cytokines, lipopolysaccharide (LPS), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), and pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-kappa B) activation, on inducible nitric oxide synthase (iNOS) expression were studied in the medullary thick ascending limb of Henle's loop cell line ST-1. LPS + interferon-gamma (IF-gamma) promoted a time-dependent increase in nitrite (a NO metabolite) and iNOS mRNA and the appearance of NF-kappa B p50 and p65 in nuclear protein extracts. Actinomycin D but not cycloheximide prevented the LPS + IF-gamma induction of iNOS mRNA and NO synthesis, indicating that iNOS transcriptional activation by LPS + IF-gamma does not require newly synthesized proteins. PDTC inhibited the LPS + IF-gamma induction of NO, iNOS mRNA, and the appearance of NF-kappa B in nuclear protein extracts, suggesting that NF-kappa B mobilization and trans-activation of the iNOS gene mediates this induction. In contrast to other cell types, cycloheximide did not alter iNOS mRNA stability, and 8-BrcAMP did not alter basal or LPS+IF-gamma induced NO production in ST-1 cells.

8-Bromo Cyclic Adenosine Monophosphate↗

Differential expression and induction of mRNAs encoding two inducible nitric oxide synthases in rat kidney.

We used quantitative PCR methods and renal microdissection to characterize the expression of inducible nitric oxide synthase (iNOS) mRNAs in rat kidney and cultured glomerular mesangial cells. A partial cDNA homologous to murine macrophage iNOS (macNOS), but distinct from rat vascular smooth muscle iNOS (vsmNOS), was cloned from normal rat kidney. macNOS was the principal iNOS isoform tonically expressed in microdissected glomeruli, proximal tubules, medullary thick ascending limbs (mTAL), cortical and inner medullary collecting ducts (IMCD), and cultured mesangial cells, whereas vsmNOS was the major isoform expressed in arcuate and interlobular arteries. Basal macNOS expression was greatest in mTALs and IMCDs. Restriction mapping of RT-PCR products indicated that basal expression of macNOS mRNA was comparable to that of vsmNOS in cortex, but greater than vsmNOS in outer and inner medulla. However, compared to controls, lipopolysaccharide (LPS)-treated rats exhibited a much greater proportion of vsmNOS mRNA and higher levels of total iNOS mRNA in each zone. Similarly, TNF alpha and IF-gamma preferentially induced expression of vsmNOS mRNA in cultured mesangial cells. We conclude that two iNOS isoforms are constitutively and heterogeneously expressed in the normal rat kidney, and that endotoxemia and cytokines differentially induce their expression.

Amino Acid Oxidoreductases↗

In situ hybridization localization of mRNA encoding inducible nitric oxide synthase in rat kidney.

We used in situ hybridization with a digoxigenin-labeled cRNA for inducible nitric oxide synthase (iNOS) to characterize the intrarenal distribution of iNOS transcripts in normal and lipopolysaccharide (LPS)-treated rats. In normal rats, the S3 segment of the proximal tubule, the cortical and medullary thick ascending limb, the distal convoluted tubule, and the cortical and inner medullary collecting duct were intensely labeled, whereas the thin limbs of Henle, proximal convoluted tubule, outer medullary collecting duct, and medullary interstitial cells were weakly labeled. LPS-treated rats exhibited a similar labeling pattern, but with increased staining of mesangial cells, medullary interstitial cells, and papillary surface epithelium. The renal vasculature, including the afferent arteriole, was not labeled in either group. No cellular labeling was observed when the sections were hybridized with the sense iNOS probe. These results indicate that iNOS mRNA is tonically and differentially expressed along the normal rat nephron and that LPS induces iNOS gene expression in normally quiescent mesangial cells, medullary interstitial cells, and papillary surface epithelium.

Amino Acid Oxidoreductases↗

Effects of thromboxane A2 receptor blockade on oliguric ischemic acute renal failure in conscious rats.

To investigate the potential pathogenetic and therapeutic roles of thromboxane A2 (TXA2) and its receptor blockade, respectively, in the early phase of ischemic acute renal failure (ARF), renal function, TXB2 excretion, and the effects of the specific TXA2 receptor antagonist sulotroban (SU) in a model of unilateral renal artery occlusion in conscious female Sprague-Dawley rats were studied. Occlusion of the left renal artery for 1 h in untreated (i.e., vehicle-treated) rats (N = 8) resulted in oliguric ARF. In SU-treated rats (N = 8), the drug was given as an i.v. bolus of 5 mg/kg body wt, followed by a continuous infusion of 0.5 mg/min.kg body wt from 1 h before and during ischemia and for 6 h after reflow. After 1 h of ischemia, urine volume of left ischemic kidneys from untreated rats had decreased from 13.2 +/- 2.8 to 1.0 +/- 0.3 and 0.5 +/- 0.2 microL/min.100 g at 2 and 6 h of reflow, respectively, and GFR had decreased from 0.32 +/- 0.04 mL/min.100 g body wt to undetectable values. At 6 h of reflow, medullary Na-K-ATPase was slightly (P < 0.05) reduced in left ischemic kidneys, whereas medullary and papillary enzyme activities were compensatorily increased (P < 0.01) in right intact kidneys. The ADP/O ratio of cortical mitochondria was 41% (P < 0.05) and ATP synthesis was 77% (P < 0.01) lower than in right intact kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗