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Biomedical subjects

G Baumann

Publications and source records attributed to G Baumann.

At least 73 records · Page 4Linked to original sources
PubMed2000

Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.

Adult↗
PubMed2000

Late results of mitral valve reconstruction in the elderly.

BACKGROUND: This study attempts to confirm favorable results with mitral valve reconstruction (MVP) in patients greater than or equal to 70 years of age and to examine complication rates by actual analysis. METHODS: Between June of 1980 and December of 1997, 278 patients 70 years of age or older (mean, 75.2 years; range, 70 to 87 years) underwent MVP for mitral regurgitation. Most involved insertion of an annuloplasty ring. Concomitant procedures were performed in 72.3%, and 55.0% required coronary revascularization. RESULTS: For isolated MVP, the in-hospital mortality rate was 6.5% and 17.0% when combined with coronary revascularization. The mortality rate when combined with another valve procedure was 13.2%. The 5-year freedom from late cardiac death was 100% in the isolated MVP group and 79.7% for MVP with a concomitant procedure (p = 0.006). Complications were analyzed using actual (cumulative incidence) analysis to eliminate the competing risk of noncardiac death. Mean NYHA class improved from 3.32 to 1.71 postoperatively. Repair failure was rare, with a 5-year freedom from reoperation of 91.2%. CONCLUSIONS: These findings confirm the favorable outcome of MVP in elderly patients. Late repair failures are rare; comorbid disease is an important predictor of outcome.

Aged↗
PubMed2000

Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: three-month results from a randomized study.

OBJECTIVES: The objective of our study was to assess the hemodynamic effects of immunoadsorption (IA) and subsequent immunoglobulin G (IgG) substitution in comparison with the effects of conventional medical treatment in patients with dilated cardiomyopathy (DCM). BACKGROUND: Various circulating cardiac autoantibodies have been detected among patients suffering from DCM. These antibodies are extractable by IA. METHODS: Patients with DCM (n = 18, New York Heart Association III-IV, left ventricular ejection fraction <30%) and who were on stable medication participated in the study. Hemodynamic measurements were performed using a Swan-Ganz thermodilution catheter. The patients were randomly assigned either to the treatment group with IA and subsequent IgG substitution (IA/IgG group, n = 9) or to the control group without IA/IgG (n = 9). In the IA/IgG group, the patients were initially treated in one IA session daily on three consecutive days. After the final IA session, 0.5 g/kg of polyclonal IgG was substituted. At one-month intervals, IA was then repeated for three further courses with one IA session daily on two consecutive days, until the third month. RESULTS: After the first IA course and IgG substitution, cardiac index (CI) increased from 2.1 (+/-0.1) to 2.8 (+/-0.1) L/min/m2 (p < 0.01) and stroke volume index (SVI) increased from 27.8 (+/-2.3) to 36.2 (+/-2.5) ml/m2 (p < 0.01). Systemic vascular resistance (SVR) decreased from 1,428 (+/-74) to 997 (+/-55) dyne x s x cm(-5) (p < 0.01). The improvement in CI, SVI and SVR persisted after three months. In contrast, hemodynamics did not change throughout the three months in the control group. CONCLUSIONS: Immunoadsorption and subsequent IgG substitution improves cardiovascular function in DCM.

Adult↗
PubMed2000

Oxidative stress in the human heart is associated with changes in the antioxidative defense as shown after heart transplantation.

The study was designed to demonstrate--for the first time in humans--that oxidative stress in the heart indicated by lipid peroxidation is associated with time-dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial biopsies (taken between the fifth day and 6 years after transplantation) of 31 heart transplant recipients who were suspected of suffering from increased formation of oxygen radicals in the allograft. The levels of lipid peroxides (LPO), glutathione peroxidase (GSH-Px), total-, copper/zinc- and manganese superoxide dismutase (t-SOD, CuZnSOD, MnSOD) were compared in 3 post-transplantation periods (5-90 d vs. 91-365 d vs. >1 y). Significantly increased LPO levels were found (0.27+/-0.04 vs. 0. 13+/-0.02 vs. 0.27+/-0.04 nmol/mg protein) in the first and third period. Increased activities of GSH-Px (39.8+/-3.8 vs. 30.2+/-4.1 vs. 76.7+/-6.5 mU/mg protein), t-SOD (1.57+/-0.10 vs. 1.30+/-0.14 vs. 2.44+/-0.23 U/mg protein) and CuZnSOD (1.09+/-0.08 vs. 0.93+/-0.13 vs. 2.05+/-0.21 U/mg protein) occurred only in the third period. For calculation of time courses more precisely, the single data with respect to time were analyzed with a curve fitting program. Except for the first period, the allograft LPO and GSH-Px levels rose for up to 6 years after transplantation. However, the t-SOD and CuZnSOD activities switched from increase to decrease in the third period. The study provided indication for: first, the potency of the human heart to time-limited increase of the enzymatic antioxidative defense, and secondly, the inability of human heart allografts--despite this adaptation--for complete prevention of myocardial oxidative stress.

Adult↗
PubMed2000

Combined treatment with ramipril and metoprolol prevents changes in the creatine kinase isoenzyme system and improves hemodynamic function in rat hearts after myocardial infarction.

Beneficial effects of monotherapy with ACE inhibitors or beta-blockers on hemodynamic function after myocardial infarction are well known. Until now, the effects of combined treatment on cardiac function and energy metabolism have been poorly described. This study examines the effects of combined ramipril and metoprolol treatment on the creatine kinase (CK) system and hemodynamic function in rats after infarction. Wistar rats with experimental infarction were randomized for treatment with ramipril (R), metoprolol (M), combined treatment (MR), or placebo (P). Sham-operated (SO) animals served as controls. After 6 weeks, we assayed for CK isoenzymes and performed hemodynamic measurements. In P versus SO, left ventricular systolic pressures (dp/dt(max) and dp/dt(min)) diminished, whereas left ventricular end-diastolic pressure (LVEDP) increased. Decreased total CK activity and mitochondrial CK isoenzyme, increased CK-MB, and increased CK-BB isoenzymes were measured in P versus SO. With infarct size < or =45%, mitochondrial CK increased in M and R versus P. Combined treatment had an additional enhancing effect on mitochondrial CK isoenzyme level versus M and R, decreased LVEDP versus P, as well as increased dp/dt(max) and dp/dt(min) versus R. These results provide evidence of an interaction between normalization of energy metabolism and improvement in cardiac function due to a combination of ACE inhibition and beta blockade after myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed2000

Elevated serum leptin in patients with coronary artery disease: no association with the Trp64Arg polymorphism of the beta3-adrenergic receptor.

BACKGROUND: Serum leptin is associated with the occurrence of cardiovascular risk factors but it is unknown whether leptin is also associated with cardiovascular disease. Another open question is whether the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) is a determinant of circulating leptin. OBJECTIVES: We measured serum leptin concentrations in a large group of patients with angiographically assessed coronary artery disease (CAD) and investigated the relationship between the Trp64Arg polymorphism of the beta3-adrenergic receptor (AR) and serum leptin. PATIENTS AND METHODS: Leptin was measured in the fasting state in 1000 consecutive patients with angiographically confirmed CAD by radioimmunoassay. The codon 64 T/C polymorphism of the beta3-AR gene was analysed by the polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) technique. Controls were 1000 age-, gender- and weight-matched subjects without clinical signs of CAD. RESULTS: Serum leptin concentrations were significantly higher in patients with CAD than in those without CAD (median: 6.8 vs 6.1 ng/ml, P < 0.001). In a multiple regression analysis leptin was found to be a determinant of CAD (P = 0.005) along with established risk factors. No differences in serum leptin were observed between wild-type and heterozygous carriers of the Trp64Arg mutation of the beta3-AR gene, whereas the small group of homozygous carriers had higher leptin due to their higher BMI. In a multiple linear regression analysis, body mass index, gender and fasting insulin were the main significant determinants of serum leptin, whereas the beta3-AR polymorphism had no effect. CONCLUSIONS: Patients with coronary artery disease exhibit higher serum leptin concentrations than age- and gender-matched controls of comparable BMI, indicating that leptin could contribute to the development of cardiovascular disease, possibly via activation of the sympathetic nervous system. The Trp64Arg variant of the beta3-adrenoceptor did not influence serum leptin.

Aged↗
PubMed2000

Immunoadsorption in dilated cardiomyopathy.

The prognosis for patients suffering from advanced stages of dilated cardiomyopathy (DCM) is poor. Recent studies have shown that immunoadsorption (IA) may represent an effective alternative therapeutic approach for other kinds of autoimmune diseases with circulating autoantibodies. The objective of this pilot study was to ascertain the short-term hemodynamic effects of IA in patients with idiopathic DCM and circulating autoantibodies. Our study included 9 patients with circulating beta1-adrenoreceptor antibodies who suffered from idiopathic DCM as well as severe heart failure (left ventricular ejection fraction <30%). Immunoadsorption was performed on 5 consecutive days using an adsorber against immunoglobulins (Ig Therasorb, Baxter, Unterschleissheim, Germany). Substitution of 0.5 g/kg of polyclonal immunoglobulin took place after the final IA session. During IA, the cardiac index and stroke volume index increased from 2.0+/-0.42 to 2.9+/-0.79 L/min(-1)/m(-2), p < 0.01, and from 24.0+/-7.4 to 35.9+/-10.3 ml/m2, p < 0.05, respectively. In addition to drug therapy, IA may represent a promising alternative therapeutic possibility for hemodynamic stabilization of patients with severe idiopathic DCM.

Adult↗
PubMed2000

A1166C polymorphism of the angiotensin II type 1 receptor gene and risk of adverse events after coronary catheter interventions.

BACKGROUND: Contradictory reports exist concerning the role of the angiotensin II type 1 receptor A1166C polymorphism as a coronary risk factor. Moreover, it is unknown whether the A1166C polymorphism is associated with thrombotic complications after coronary catheter interventions. METHODS: We investigated the role of the A1166C polymorphism as a risk factor in 1000 patients with coronary artery disease (CAD) and in 1000 age- and sex-matched controls. A total of 649 patients receiving interventions (270 coronary angioplasty, 102 atherectomy, and 277 stenting) were investigated for a 30-day composite end point including target vessel revascularization, myocardial infarction, or death. RESULTS: The composite end point was reached by 42 patients (6.5%) without evidence that the C allele was associated with excess procedural risk (odds ratio 0.93; 95% confidence interval 0.79-1.75; P =.82). Further analyses by device failed to show linkage with adverse events complicating coronary angioplasty, atherectomy, and stenting. Moreover, in the entire CAD group (n = 1000), the polymorphism even showed a trend to underrepresentation (odds ratio 0.83; 95% confidence interval 0.69-1. 004, P =.054). CONCLUSIONS: These results indicate that the A1166C polymorphism neither represents a risk factor for adverse events complicating coronary interventions nor seems to have significant impact on further long-term processes such as development and severity of CAD.

Aged↗
PubMed2000

Stimulation of pulmonary big endothelin-1 and endothelin-1 by antithrombin III: a rationale for combined application of antithrombin III and endothelin antagonists in sepsis-related acute respiratory distress syndrome?

OBJECTIVES: Antithrombin (AT) III reduces lung damage in animal models of septic acute respiratory distress syndrome (ARDS), which is generally attributed to stimulation of endothelial prostacyclin synthesis. However, clinical studies have failed so far to demonstrate mortality reduction by application of AT III. We investigated whether AT III stimulates pulmonary prostacyclin release. In addition, we hypothesized that it may promote pulmonary endothelins, thereby mitigating its own protective effect in the course of ARDS. DESIGN: Controlled experiment using isolated organs. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Isolated lungs were perfused over 120 mins in recirculatory mode in the presence of 50 microg/mL endotoxin (n = 11), 2U/mL AT III (n = 10), 5 U/mL AT III (n = 13), endotoxin plus 2 U/mL AT III (n = 5), or vehicle alone (controls, n = 13), respectively. MEASUREMENTS AND MAIN RESULTS: We determined the effects of AT III on vascular release of thromboxane B2, 6-keto-prostaglandin-F1alpha, big endothelin-1, and endothelin-1. Control lungs released 59+/-23 pg/mL thromboxane B2, 1,480+/-364 pg/mL 6-keto-prostaglandin-F1alpha, 15.2+/-4.5 pg/mL big endothelin-1, and 0.46+/-0.13 pg/mL endothelin-1. Exposure to endotoxin increased thromboxane B2 release 2.9-fold, 6-keto-prostaglandin-F1alpha release 1.6-fold, and endothelin-1 1.6-fold (p < .05 each); levels of big endothelin-1 were unchanged. AT III at 2 U/mL elevated production of big endothelin-1 (1.7-fold) and endothelin-1 (1.2-fold) (p < .05 for both). AT III at 5 U/mL enhanced levels of big endothelin-1 (1.6-fold) and endothelin-1 (1.3-fold) (p < .05 for both). Neither dose of AT III affected thromboxane B2 or 6-keto-prostaglandin-F1alpha concentrations. Application of 2 U/mL AT III plus endotoxin stimulated big endothelin-1 production (2.6-fold) compared with endotoxin or AT III alone (p < .05 for both), but did not further elevate endothelin-1 release. CONCLUSIONS: AT III does not stimulate pulmonary prostacyclin, but promotes pulmonary release of big endothelin-1 and endothelin-1 under basal and, particularly, under septic conditions, which may blunt the AT III-induced lung protection during ARDS. Therefore, we suggest combined application of AT III and endothelin antagonists in animal models of septic ARDS.

Analysis of Variance↗
PubMed2000

Oxygen radical system in chronic infarcted rat heart: the effect of combined beta blockade and ACE inhibition.

In vitro experiments suggest that beta blockade and angiotensin-converting enzyme (ACE) inhibition may protect the failing heart by reduction of myocardial oxidative stress. To test this hypothesis in an in vivo model, the beta blocker metoprolol (350 mg) and the ACE inhibitor ramipril (1 mg) were given either alone or in combination to rats (per kilogram body weight per day) for 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP), contractile function of papillary muscles, enzymatic antioxidative defense (indicated by the activities of the superoxide dismutase isoenzymes and glutathione peroxidase), and the extent of lipid peroxidation were studied. Placebo-treated rats showed cardiac hypertrophy, increased LVEDP, lower rates of contraction and relaxation, as well as a deficit in the myocardial antioxidative defense associated with increased lipid peroxide levels, when compared with sham-operated animals. Combined beta blockade and ACE inhibition improved the antioxidative defense, reduced hypertrophy and LVEDP, and enhanced rates of contraction. Thus prolonged beta blockade and ACE inhibition after infarction may decrease myocardial oxidative stress and thereby could be beneficial in heart failure.

Adrenergic beta-Antagonists↗
PubMed2000

High CA repeat numbers in intron 13 of the endothelial nitric oxide synthase gene and increased risk of coronary artery disease.

Endothelial nitric oxide synthase (eNOS) plays a key role in vascular homeostasis. Because its product, nitric oxide, possesses vasodilatory and antiatherogenic properties, an altered eNOS function might promote atherosclerosis. We investigated the association between variations in CA repeat copy number [(CA), polymorphism] in intron 13 of the eNOS gene and the risk of coronary artery disease. (CA), polymorphism was investigated in 1000 consecutive patients with angiographically confirmed coronary artery disease and 1000 age- and gender-matched control subjects by a PCR-based fragment length calculation. Twenty-eight different alleles were identified containing 17-44 CA repeats. The presence of one allele containing > or = 38 repeats was associated with an excess risk of coronary artery disease (odds ratio 1.94, 95% confidence interval 1.31-2.86, P = 0.001). Carriers of alleles containing > or = 38 CA repeats were, in particular, overrepresented in the subgroup without common cardiovascular risk factors (odds ratio 3.39, 95% confidence interval 1.30-8.86, P = 0.009). Logistic regression analysis revealed that the (CA), polymorphism proved to be an independent risk factor (relative risk 2.17, 95% confidence interval 1.44-3.27, P = 0.0002). Our findings indicate that high numbers of CA repeats in intron 13 of the eNOS gene are associated with an excess risk of coronary artery disease.

Adenine↗
PubMed2000

P wave and far-field R wave detection in pacemaker patient atrial electrograms.

This study was undertaken to develop and test a morphology-based adaptive algorithm for real-time detection of P waves and far-field R waves (FFRWs) in pacemaker patient atrial electrograms. Cardiac event discrimination in right atrial electrograms has been a problem resulting in improper atrial sensing in implantable devices; potentially requiring clinical evaluation and device reprogramming. A morphology-based adaptive algorithm was first evaluated with electrograms recorded from 25 dual chamber pacemaker implant patients. A digital signal processing (DSP) system was designed to implement the algorithm and test real-time detection. In the second phase, the DSP implementation was evaluated in 13 patients. Atrial and ventricular electrograms were processed in real-time following algorithm training performed in the first few seconds for each patient. Electrograms were later manually annotated for comparative analysis. The sensitivity for FFRW detection in the atrial electrogram during off-line analysis was 92.5% (+/- 10.9) and the positive predictive value was 99.1% (+/- 1.8). Real-time P wave detection using a DSP system had a sensitivity of 98.9% (+/- 1.3) and a positive predictivity of 97.3% (+/- 3.5). FFRW detection had a sensitivity of 91.0% (+/- 12.4) and a positive predictivity of 97.1% (+/- 4.2) in atrial electrograms. DSP algorithm tested can accurately detect both P waves and FFRWs in right atrium real-time. Advanced signal processing techniques can be applied to arrhythmia detection and may eventually improve detection, reduce clinician interventions, and improve unipolar and bipolar lead sensing.

Adolescent↗
PubMed2000

Coronary artery bypass grafts: improved electron-beam tomography by prolonging breath holds with preoxygenation.

In 45 patients with coronary bypass grafts, the breath-hold interval with and that without preoxygenation was measured. Its effect on depiction of the distal graft anastomosis at electron-beam tomography was evaluated. Preoxygenation prolonged the breath-hold interval in most patients, thereby allowing greater anatomic coverage including more distal anastomoses. Preoxygenation may improve scanning of coronary bypass grafts and increase detectability of graft stenoses.

Adult↗
PubMed2000

Sleep apnea syndrome in patients with cardiac pacemaker.

BACKGROUND: Heart rhythm disturbances are cardiac side effects in patients with sleep-disordered breathing (SDB), which in itself is considered to be a risk factor for bradycardic rhythm disturbances. OBJECTIVE: We analyzed the prevalence and degree of SDB in patients who received a cardiac pacemaker due to bradycardic rhythm disturbances and investigated the relationship between the severity of an underlying SDB and the type of heart rhythm disturbance. METHODS AND RESULTS: 192 patients (100 males, 92 females, mean age 62.2 +/-12.2 years) were studied using the portable screening device MESAM IV. The respiratory disturbance index (RDI) was calculated visually. The mean RDI in all patients was 9.13+/-11. 09/h, 11.7+/-13.15/h in males and 6.33+/-7.42/h in females. The prevalence ratio of SDB between men and women was 1.7:1, with significant differences in the respective severity (p<0.05). The screening showed a prevalence of SDB (RDI >10/h) of 32.3%. The highest prevalence was found in the group of patients with atrial fibrillation and bradycardia. However, there were no significant differences compared to other types of rhythm disturbances. The RDI in the population studied depended on age and body mass index, but not on the existence or type of rhythm disturbance and not on concomitant diseases. CONCLUSION: The prevalence of SDB in cardiac pacemaker patients is similar to that in patients of comparable age without a pacemaker. A heart rhythm disturbance does not seem to be an independent risk factor for development of SDB. Nevertheless, the differential diagnosis of bradycardic rhythm disturbances in this age group should include a screening for sleep apnea.

Age Distribution↗
PubMed2000

Tumor necrosis factor-alpha converting enzyme (TACE) is a growth hormone binding protein (GHBP) sheddase: the metalloprotease TACE/ADAM-17 is critical for (PMA-induced) GH receptor proteolysis and GHBP generation.

The GH binding protein (GHBP), which exists in many vertebrates, is a circulating high affinity binding protein corresponding to the extracellular domain of the GH receptor (GHR). In humans, rabbits, and several other species, the GHBP is generated by proteolysis of the GHR and shedding of its extracellular domain. We previously showed that GHBP shedding is inducible by the phorbol ester phorbol 12-myristate,13-acetate (PMA) and inhibited by the metalloprotease inhibitor, Immunex Corp. Compound 3 (IC3). The metzincin metalloprotease, tumor necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE), catalyzes the shedding of TNF-alpha from its transmembrane precursor, a process that is also inhibitable by IC3. TACE may hence be a candidate for GHBP sheddase. In this study, we reconstitute fibroblasts derived from a TACE knockout mouse (Null cells) with either the rabbit (rb) GHR alone (Null/R) or rbGHR plus murine TACE (Null/R+T). Although GHR in both cells was expressed at similar abundance, dimerized normally and caused JAK2 activation in response to GH independent of TACE expression, PMA was unable to generate GHBP from Null/R cells. In contrast, PMA caused ample GHBP generation from TACE reconstituted (Null/R + T) cells, and this GHBP shedding was substantially inhibited by IC3 pretreatment. Corresponding to the induced shedding of GHBP from Null/R + T cells, PMA treatment caused a significant loss of immunoblottable GHR in Null/R+T, but not in Null/R cells. We conclude that TACE is an enzyme required for PMA-induced GHBP shedding and that PMA-induced down-regulation of GHR abundance may in significant measure be attributable to TACE-mediated GHR proteolysis.

ADAM Proteins↗
PubMed2000

Pituitary hypoplasia in patients with a mutation in the growth hormone-releasing hormone receptor gene.

BACKGROUND AND PURPOSE: Several anatomic abnormalities of the pituitary gland have been described as occurring in association with congenital growth hormone deficiency, including hypoplasia of the adenohypophysis, truncation of the pituitary stalk, and ectopia of the neurohypophysis. Their pathogenesis, however, is obscure. Normal pituitary development is dependent on the sequential expression of a series of ontogenetic factors. Growth hormone-releasing hormone (GHRH) is known to stimulate somatotroph proliferation, and a dwarf mouse model with a mutant GHRH receptor, the "little mouse," has a small anterior pituitary due to hypoplasia of the somatotrophs. We recently described the human homolog of the little mouse (dwarfism of Sindh), caused by a homozygous nonsense mutation in the GHRH receptor gene in a Pakistani kindred. We investigated MR imaging characteristics to gain information regarding the potential role of GHRH in human pituitary organogenesis. METHODS: MR images of the head were obtained of four affected male patients (age range, 22-29 years). Maximal anterior pituitary dimensions were determined from sagittal and coronal images, and pituitary volumes were estimated from cubic and ellipsoid formulae. The measurements were compared with normative values matched for age and sex. RESULTS: The adenohypophysis was small in each of the four patients. The maximal height for the anterior pituitary was 3 mm in three patients and 2 mm in one (mean +/- SD, 2.75 +/- 0.5 mm), which is significantly (P < .001) less than the expected height of 5.6 +/- 1.0 mm for men in this age group. Estimates of anterior pituitary volume in the patients ranged from 75 to 124 mm3 (104 +/- 21 mm3), which corresponds to 35% to 52% of the normal mean volume corrected for small head size (P < .005). No other cranial abnormalities were identified. CONCLUSION: We describe significant hypoplasia of the adenohypophysis occurring in four dwarfs with a nonsense mutation in the GHRH receptor. In addition to isolated growth hormone deficiency and severe dwarfism, affected patients have anterior pituitary hypoplasia, presumably due to somatotroph maldevelopment. Resistance to GHRH explains the hypoplasia of the adenohypophysis--a feature that contributes to growth hormone deficiency in this syndrome. This is one of the few instances in which the molecular basis of pituitary dysmorphogenesis has been identified.

Adult↗
PubMed2000

[Biatrial pacing as an effective therapy method of paroxysmal atrial fibrillation].

For effective management of drug-refractory atrial fibrillation as the most common arrhythmia new methods are needed. In case of existing interatrial conduction disturbance the use of biatrial pacemaker with standard right atrial lead and additive coronary sinus lead for left atrial pacing shows an antiarryhthmic effect due to atrial resynchronisation. In order to demonstrate the antiarrhythmic effect of biatrial pacing, 74 pts. (26 f/48 m, mean age 63 +/- 9.4 y, follow-up 482 +/- 183 days) received a biatrial pacemaker (AAD-mode, AV-delay 0 msec, LOGOS, Fa. Biotronik) from 11/97 to 03/99. All patients had a prolongation of P-wave duration more than 100 msec (mean 122.3 +/- 23.1 msec). Preoperatively 9/74 (12%) pts. had monthly, 49/74 pts. (66%) had weekly, and 11/74 pts. (15%) had daily episodes of atrial fibrillation. Permanent atrial fibrillation > 6 month was seen in 5/74 pts. (7%, preoperative cardioversion). The intraoperative right atrial pacing threshold was 0.89 +/- 0.64 V (0.5 msec pulse width), the atrial signal amplitude 2.31 +/- 1.03 mV, the impedance signal 616 +/- 157 omega. Voltage recording in the coronary sinus showed a pacing threshold of 1.4 +/- 0.68 V (0.5 msec pulse width) and a potential of 3.47 +/- 1.44 mV. The impedance signal was 559 +/- 137 omega. The obtained P-wave duration was reduced for 33.9 +/- 20.1 msec. In 7/74 pts. (9.4%) we found a dislocation and in 4/74 pts. (5.4%) an excessive high pacing threshold of coronary sinus lead > 4 V/0.5 msec. All pts. with dislocated lead were reoperated. There were no perforations and thromboses of coronary sinus. The intervention led to a significant inhibition of atrial fibrillation in 11/74 pts. (14.9%) without and in 17/74 pts. (24.3%) with antiarrhythmic drugs. 17/74 pts. (24.3%) had a reduction of episodes without and 16/74 pts. (21.6%) with concomitant medication. The treatment did not have any influence on the prevalence of atrial fibrillation in 9/74 pts. (27%). In conclusion, the implantation of biatrial pacemaker leads to a significant reduction of atrial fibrillation episodes and has proven to be practicable and safe for clinical use.

Aged↗