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Biomedical subjects

R Meyer

Publications and source records attributed to R Meyer.

At least 91 records · Page 5Linked to original sources

Premature closure of foramen ovale and renal vein thrombosis in a stillborn twin homozygous for methylene tetrahydrofolate reductase gene polymorphism: a clinicopathologic case study.

Premature closure of the foramen ovale, 4-chamber cardiac hypertrophy, and renal vein/vena cava thrombosis were found at autopsy of a stillborn dizygotic twin at 36 weeks gestational age. Review of the original prenatal sonograms showed features suggestive of early closure of the foramen ovale. Homozygosity for the 5, 10 methylene tetrahydrofolate reductase mutation was shown only in the affected twin after the parents were found to be heterozygous for the mutation. The difference in outcome of the twins following prenatal treatment with beta mimetics and corticosteroids for preterm labor may be related to the added susceptibility factor for thromboembolism associated with presumed hyperhomocysteinemia in the proband which was not shared by the surviving healthy twin. The role of premature closure of the foramen ovale and prenatal treatment are discussed but remain uncertain.

Cardiomegaly↗

Safety and biodistribution of 99mTechnetium-labeled anti-CD44v6 monoclonal antibody BIWA 1 in head and neck cancer patients.

The CD44 protein family consists of isoforms, encoded by standard exons and up to nine alternatively spliced variant exons (v2-v10), which are expressed in a tissue-specific way. Expression of v6-containing variants (CD44v6) has been related to aggressive behavior of various tumor types and was shown to be particularly high in squamous cell carcinoma (SCC). Therefore, CD44v6 might be a suitable target for radioimmunoscintigraphy (RIS) and therapy. The present study evaluates the novel high-affinity murine anti-CD44v6 monoclonal antibody (MAb) BIWA 1 for its safety and targeting potential in patients with SCC of the head and neck (HNSCC). Twelve HNSCC patients, who had planned to undergo resection of the primary tumor and neck dissection, were included. Preoperatively, 2, 12, or 52 mg of 99nTc-labeled MAb BIWA 1 was administered. RIS results obtained 21 h after injection were compared with palpation, computed tomography, and magnetic resonance imaging, with histopathology as the gold standard. Moreover, biodistribution of BIWA 1 was evaluated by radioactivity measurement in blood and bone marrow and in biopsies from the surgical specimen obtained 40 h after injection. The distribution of BIWA 1 in tumor biopsies was analyzed by immunohistochemistry. BIWA 1 integrity in the blood was assessed by high-performance liquid chromatography and related to soluble CD44v6 levels in serum samples. No drug-related adverse events were observed. Human antimouse antibody responses were observed in 11 patients. The diagnostic efficacy of RIS appeared to be comparable for the three BIWA 1 dose levels and for the four diagnostic methods. Besides activity uptake in tumor tissue, minimal accumulation of activity was observed in mouth, lungs, spleen, kidney, bone marrow, and scrotal area. Analysis of tissue biopsies revealed high uptake in tumors, with a mean value of 14.2+/-8.4% of the injected dose/kg tumor tissue and a mean tumor:blood ratio of 2.0+/-1.4 at 40 h after injection. Differences among the three dose groups were not statistically significant, although a trend toward lower uptake in the highest dose group was noted. Distribution of BIWA 1 throughout the tumor was heterogeneous for all dose groups, which might be related to the high affinity of the MAb. The mean biological half-life in blood (34.5+/-6.1 h) was not dose dependent. Extensive complex formation of BIWA 1 was observed in the 2-mg group, most probably with soluble CD44v6 present in the blood, and complex formation relatively diminished upon increase of the MAb dose. BIWA 1 is a promising MAb for targeting HNSCC because it can be safely administered to HNSCC patients, while it shows high and selective tumor uptake. However, BIWA 1 is immunogenic, and therefore a chimerized or humanized derivative of BIWA 1 with intermediate affinity will be used in future clinical trials.

Adult↗

[Alcohol--risk factor for overweight].

Overweight is accepted as risk factor for various diseases such as hypertension and diabetes mellitus, dyslipidemias and cardiovascular diseases. In this study the correlation of alcohol consumption and overweight was investigated among members of the Swiss association of inn keepers and hotel managers (Gastrosuisse). A questionnaire was mailed to all members of the Gastrosuisse in the cantons of Zürich, Graubünden, and the German speaking part of Freiburg. The following parameters were assessed: sex, birth date, weight, height, and cardiovascular risk factors. The frequency of alcohol consumption per week, the type and amount of alcoholic beverage (wine, beer, liquor) consumed for each drinking occasion were asked for. The daily alcohol intake (g/d) was computed. The health status, physical activity levels at work and for recreational activities, tendency for abdominal fat accumulation, self-judged stress, fat content of the diet were assessed with visual analogue scales. The present analysis was limited to non-smoking men (n = 573). A j-shaped relationship was found between alcohol consumption and the body weight: the lowest body weight was found in subjects with a mean daily consumption between 13 and 36 g/d (26.3 +/- 0.3 and 26.2 +/- 0.4 kg/m2, mean +/- sem). Non-consumers and subjects with an intake > 36 g/d had a higher body weight. The relationship was independent of age and physical activity levels as well as the beverage type. Limiting the analysis to daily alcohol consumers only a linear relationship was found. Our data suggest that alcohol consumption, especially daily consumption, should be regarded as a risk factor for an increased body weight and obesity.

Adult↗

Identification of ether à go-go and calcium-activated potassium channels in human melanoma cells.

Ion channels and intracellular Ca2+ are thought to be involved in cell proliferation and may play a role in tumor development. We therefore characterized Ca(2+)-regulated potassium channels in the human melanoma cell lines IGR1, IPC298, and IGR39 using electrophysiological and molecular biological methods. All cell lines expressed outwardly rectifying K+ channels. Rapidly activating delayed rectifier channels were detected in IGR39 cells. The activation kinetics of voltage-gated K+ channels in IRG1 and IPC298 cells displayed characteristics of ether à go-go (eag) channels as they were much slower and depended both on the holding potential and on extracellular Mg2+. In addition, they could be blocked by physiological concentrations of intracellular Ca2+. In accordance with these electrophysiological results, analysis of mRNA revealed the expression of a gene coding for h-eag1 channels in IGR1 and IPC298 cells, but not in IGR39 cells. At elevated Ca2+ concentrations various types of Ca(2+)-activated K+ channels with single-channel characteristics similar to IK and SK channels were detected in IGR1 cells. The whole-cell Ca(2+)-activated K+ currents were not voltage dependent, insensitive for 100 nm apamin and 200 microm d-tubocurarine, but were blocked by charybdotoxin (100 nm) and clotrimazole (50 nm). Analysis of mRNA revealed the expression of hSK1, hSK2, and hIK channels in IGR1 cells.

Calcium↗

17 Beta-estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo.

OBJECTIVES: NO production has been attributed to play a major role in cardiac diseases such as cardiac hypertrophy and cardiac remodeling after myocardial infarction which display significant gender-based differences. Therefore we assessed the effect of 17 beta-estradiol (E2) on estrogen receptor (ER) alpha and beta and endothelial and inducible NO synthase in neonatal and adult rat cardiomyocytes. METHODS: The presence of ER alpha and ER beta was demonstrated by immunofluorescence and western blot analysis as well as the expression pattern of inducible NO synthase (iNOS) and endothelial NOS (eNOS) in isolated cardiomyocytes from neonatal and adult rats. Furthermore, regulation of myocardial iNOS and eNOS expression by estrogen was evaluated in the myocardium from ovariectomized or sham-operated adult Wistar-Kyoto rats. RESULTS: Incubation with E2 led to translocalization of the ER into the nucleus and increased receptor protein expression. E2 stimulated expression of iNOS and eNOS in both neonatal and adult cardiac myocytes. Coincubation with the pure anti-estrogen ICI 182,780 inhibited upregulation of ER and NOS expression. In ovariectomized rats myocardial iNOS and eNOS protein levels were significantly lower compared to sham-operated female animals. CONCLUSION: Taken together, these results show that E2 stimulates the expression of iNOS/eNOS in neonatal and adult cardiomyocytes in-vivo and in-vitro. These novel findings provide a potential mechanism of how estrogen may modulate NOS expression and NO formation in the myocardium.

Animals↗

Differential effects of 17beta-estradiol on mitogen-activated protein kinase pathways in rat cardiomyocytes.

Cardiac myocytes contain functional estrogen receptors, however, the effect of estrogen on growth-related signaling pathways such as mitogen-activated protein kinases (MAPK) in the pathogenesis of cardiac disease is unclear. MAPKs are critically involved in regulatory signaling pathways which ultimately lead to cardiac hypertrophy. Here we show that 17beta-estradiol (E2) activates extracellular signal-regulated kinase (ERK1/2), c-Jun-NH2-terminal protein kinase (JNK) and p38 in rat cardiomyocytes in a distinctive pattern. As shown by immunoblot analysis and phosphorylation assays, E2 (10(-9) M) induced a rapid and transient activation of ERK1/2 and a rapid but sustained increase of JNK phosphorylation. In contrast, E2 had only a marginal effect on p38 activation. Furthermore, MAPK phosphatase expression was induced by E2 and E2-stimulated expression of endothelial and inducible NO synthase was inhibited by PD 98059, an inhibitor of the ERK pathway. These novel observations may help to explain the role of estrogen in gender-based differences found in cardiac disease.

Animals↗

Identification and expression of delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium.

Despite its importance for the regulation of heart function, little is known about the isoform expression of the multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII) in human myocardium. In this study, we investigated the spectrum of CaMKII isoforms delta2, delta3, delta4, delta8, and delta9 in human striated muscle tissue. Isoform delta3 is characteristically expressed in cardiac muscle. In skeletal muscle, specific expression of a new isoform termed delta11 is demonstrated. Complete sequencing of human delta2 cDNA, representing all common features of the investigated CaMKII subclass, revealed its high homology to the corresponding rat cDNA. Comparative semiquantitative reverse transcription-polymerase chain reaction analyses from left ventricular tissues of normal hearts and from patients suffering from dilated cardiomyopathy showed a significant increase in transcript levels of isoform delta3 relative to the expression of glyceraldehyde-3-phosphate dehydrogenase in diseased hearts (101. 6+/-11.0% versus 64.9+/-9.9% in the nonfailing group; P<0.05, n=6). Transcript levels of the other investigated cardiac CaMKII isoforms remained unchanged. At the protein level, by using a subclass-specific antibody, we observed a similar increase of a delta-CaMKII-specific signal (7.2+/-1.0 versus 3.8+/-0.7 optical density units in the nonfailing group; P<0.05, n=4 through 6). The diseased state of the failing hearts was confirmed by a significant increase in transcript levels for atrial natriuretic peptide (292. 9+/-76.4% versus 40.1+/-3.2% in the nonfailing group; P<0.05, n=3 through 6). Our data characterize for the first time the delta-CaMKII isoform expression pattern in human hearts and demonstrate changes in this expression pattern in heart failure.

Adult↗

Membrane potential and currents of isolated heart muscle cells exposed to pulsed radio frequency fields.

The influence of radio frequency (RF) fields of 180, 900, and 1800 MHz on the membrane potential, action potential, L-type Ca(2+) current and potassium currents of isolated ventricular myocytes was tested. The study is based on 90 guinea-pig myocytes and 20 rat myocytes. The fields were applied in rectangular waveguides (1800 MHz at 80, 480, 600, 720, or 880 mW/kg and 900 MHz, 250 mW/kg) or in a TEM-cell (180 MHz, 80 mW/kg and 900 MHz, 15 mW/kg). Fields of 1800 and 900 MHz were pulsed according to the GSM-standard of cellular phones. The specific absorption rates were determined from computer simulations of the electromagnetic fields inside the exposure devices by considering the structure of the physiological test arrangement. The electrical membrane parameters were measured by whole cell patch-clamp. None of the tested electrophysiological parameters was changed significantly by exposure to RF fields. Another physical stimulus, lowering the temperature from 36 degrees C to 24 degrees C, decreased the current amplitude almost 50% and shifted the voltage dependence of the steady state activation parameter d(infinity) and inactivation parameter f(infinity) of L-type Ca(2+) current by about 5 mV. However, at this lower temperature RF effects (900 MHz, 250 mW/kg; 1800 MHz, 480 mW/kg) on L-type Ca(2+) current were also not detected.

Action Potentials↗

Muscle regeneration and fiber-type transformation during distraction osteogenesis.

The successful outcome of distraction osteogenesis depends in part on the adequate adaptation of the surrounding soft tissue. We characterized the adaptation of the tibialis anterior during distraction osteogenesis at different rates (0.7 and 1.4 mm/day) and amounts (15 and 30%) of lengthening. We documented the increased expression of neonatal and slow myosin heavy chain in the tibialis anterior of skeletally immature rabbits. There was neither expression of neonatal myosin heavy chain in the experimental soleus or in the slow muscle fibers of the tibialis anterior nor increased expression of slow myosin heavy chain in the soleus or gastrocnemius. The increased amount of neonatal myosin heavy chain was concentrated in the distal half of the muscle, whereas the increase in the number of fibers that were labeled with antibodies to slow myosin occurred to the same extent throughout the tibialis anterior. Electrophysiological methods showed that the tibialis anterior was functionally intact during and after distraction osteogenesis. We concluded that in the tibialis anterior of young, skeletally immature animals, distraction osteogenesis seems to induce a recapitulation of the developmental process without leading to functional changes. In addition, during distraction osteogenesis, a fiber-type transformation occurs similar to that observed in models of muscle overloading.

Animals↗

Protein kinase C affects reformation of endothelial junctions in xenopus XTH-2 cells.

Endothelial cells can reversibly be forced to suppress the formation of endothelial junctions (EJ) by cultivation in a low calcium medium. The authors localized vinculin and cadherin as marker proteins of EJ and actin as a cytoskeletal component by fluorescence microscopy, and used this cell model to study the reformation of endothelial junctions under conditions of activation and inhibition of protein kinase C (PKC). Inhibition of PKC by H-7 leads to an acceleration of EJ reformation, while constitutive activation by TPA inhibits the reformation process.

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

[Extracranial meningioma of the parotid gland].

Extracranial meningiomas of the head and neck region are very rare, although secondary extracranial meningiomas beside meningiomas of primary extracranial origin have also been described. Trauma, radiation and (uncommonly) metastatic spread have been associated with the pathogenesis of secondary extracranial meningiomas. We present a case of a 53-year-old patient who required six neurosurgical interventions because of a recurrent intracranial meningioma. Further surgery was required for tumor in the left parotid gland. Histological examination of this neoplasm showed an atypical meningotheliomatous meningioma. The patient is now 17 months after surgery and is free of local recurrences or metastases.

Diagnosis, Differential↗

[Glycogenosis type IV as a seldom cause of cardiomyopathy - report about a successful heart transplantation].

We report about a 17 year old male patient with a cardiomyopathy secondary to type IV glycogenosis (Andersens disease) and class II immunoglobulin deficiency who underwent cardiac transplantation. The patient first developed symptoms of heart failure at the age of twelve. The histologic diagnosis was cardiomyopathy secondary to glycogenosis. In addition, the patient suffered recurrent pulmonary infections and developed bronchiectases in the left lower lobe. This region was atelectatic since he was eleven. The patient did have two younger brothers who died of congestive heart failure at the age of nine and ten. Neither his parents nor anybody else of his relatives had a history of heart failure or glycogenosis. Since the patient suffered recurrent cardiac decompensations with the need for catecholamines he was accepted for cardiac transplantation although several relative contraindications to transplantation such as cachexia, myopathy, immunglobulin deficiency and bronchiectases had been present. The patient was transplanted successfully. The postoperative weaning from the respirator was markedly prolonged and complicated by pulmonary infection. Furthermore, mobilization was retarded. One year after transplantation, he is in a good condition without pulmonary or systemic infection. Right ventricular endomyocardial biopsies did not show recurrence of glycogenosis in the donor organ.

Adolescent↗

Gastric gas and fluid emptying assessed by magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to characterize the volumes and rates of gastric emptying of both liquid and gas following the ingestion of beverages of varying carbonation and carbohydrate levels. Eight subjects drank 800 ml each of four test beverages in a counterbalanced order: water, a non-carbonated carbohydrate-electrolyte solution (NC), a lightly carbonated carbohydrate-electrolyte solution (PC), and a carbonated cola (CC). T2-weighted, echoplanar images (25-30 contiguous slices, 1 cm thick, 256 x 128 matrix, TE = 80, 40 cm FOV) of the abdomen were collected at minutes 3,110, 20, 30, 45, and 60 following beverage ingestion. Images were analyzed for gas and liquid volumes. Water and NC emptied the most rapidly, with half times of 21(3) and 31(3) min, respectively [mean (SE)]. PC emptied significantly slower [47 (6) min] and CC slower yet [107 (8) min]. The carbonation content of the beverage accounted for 84% of the variation in emptying time, whereas carbohydrate content did not account for any significant variation. The gastric gas volume of the CC was higher at 2 min post-ingestion compared with all other drinks; however, the rate of emptying of the gas was the same among all beverages. Significantly greater total gastric volumes (gas+ liquid) were associated with the ingestion of CC, and accordingly produced a greater severity of gastric distress, as evaluated with a gastric distress inventory. The high gastric gas volumes (approximately 600 ml) after ingestion of CC suggested a potential source of error in body composition using standard hydrostatic weighing methods. This prediction was tested in nine additional subjects. Ingestion of 800 ml of CC prior to hydrostatic weighing resulted in a 0.7% underestimate of body density and thus an 11% overestimate of percentage body fat compared to measurements made before beverage consumption.

Adult↗

A cephalometric and tomographic evaluation of Herbst treatment in the mixed dentition.

This study describes combined treatment and posttreatment effects for patients treated with the Herbst appliance in the mixed dentition followed by retention with a prefabricated positioner. The sample included 24 female and 16 male patients with Class II malocclusions. Posttreatment lateral cephalograms were taken an average of 17 months after Herbst removal, when the patients presented for phase II comprehensive orthodontics. The cumulative treatment and retention effects were compared with a sample of untreated Class II controls matched for age, sex, and mandibular plane angle. The overjet and molar relationship were corrected by 3. 4 and 3.3 mm, respectively. A headgear effect of Herbst therapy was observed, as anterior maxillary displacement was reduced by 1.2 mm. Condylar growth was redirected to produce 2.0 mm greater posterior growth in the treatment group. These effects produced significantly greater decreases in SNA (0.8 degrees ) and ANB (1.4 degrees ), and a tendency toward an increase in SNB (0.5 degrees ) Mandibular orthopedic effects resulted in an increase in anterior facial height (1.6 mm) and inferior displacement of the chin. Minimal changes in the displacement of condylion in relation to stable cranial base structures suggest that glenoid fossa displacement does not contribute in a clinically significant way to Class II correction. Pretreatment, immediate posttreatment, and postretention corrected temporomandibular joint tomograms demonstrated a tendency for the condyle to be slightly forward (0.2 mm) at the end of treatment and then to fall back after treatment. Statistically significant joint space changes were limited to the posttreatment period. We conclude that Herbst treatment in the mixed dentition, in combination with retention, produces significant long-term improvements in dental and skeletal relationships as a result of dentoalveolar changes and orthopedic effects in both jaws.

Case-Control Studies↗

Coronary artery bypass grafting after orthotopic heart transplantation.

OBJECTIVE: Graft coronary disease (GCD) remains the major determinant of long-term survival after heart transplantation. Therapeutic strategies for the prevention or retardation of GCD in the cardiac allograft are limited, and palliative surgical coronary revascularization has been attempted. The aim of this report was to retrospectively analyze our results of coronary artery bypass grafting after cardiac transplantation. This paper correlates the outcome of patients with the pathohistological and angiographic type of lesion in order to identify transplant recipients who may profit from surgical myocardial revascularization. METHODS: Seven patients with a mean age of 55 years (range 45-61 years) underwent coronary artery bypass grafting as a result of GCD at a mean of 67 months (range 6-128 months) after cardiac transplantation. By the inclusion of the clinical history and the angiographic pattern of GCD lesions, the primary indications for surgical revascularization, operative results, pathohistological studies and follow-ups were examined. RESULTS: Elective surgery was performed in two patients with proximal, severe triple vessel disease (Type A lesion) and in one patient in whom the primary reason for cardiac surgery was severe tricuspid regurgitation. This patient electively received a tricuspid valve replacement and concomitant single vessel bypass surgery for proximal GCD (Type A lesion). Emergency surgery was performed in four patients: preoperatively three patients post-infarction developed worsening congestive heart failure, which resulted in low cardiac output syndrome. One patient with combined Types A and B/C lesions required emergency surgery for dissection of the right coronary artery (RCA) after an angioplasty procedure. Angiographically all these patients showed diffuse, distal arteriopathy (combined Type B/C lesions). The electively operated patients (n = 3) and the patient with dissection of the RCA (n = 1) had successful operations and survived beyond hospital discharge (overall survival for coronary artery bypass graft (CABG) in GCD patients 4 out of 7; 57%). All three patients with distal arteriopathy, who underwent emergency surgery, died in hospital from left ventricular failure (43%). The four patients discharged from hospital with a mean follow-up of 10 months (range 2-32 months) are all in good clinical condition. CONCLUSIONS: Coronary artery bypass grafting can be successfully performed in a subgroup of cardiac transplant patients with Type A lesions. However, the state of diffusely diseased distal arteries (Type B/C lesions), which is prevalent in this group of patients, limits the use of bypass surgery.

Biopsy↗

Cognitive status, language attainment, and prereading skills of 6-year-old very preterm children and their peers: the Bavarian Longitudinal Study.

The prevalence of intellectual-, language-, and prereading-skill deficits was investigated in a geographically defined whole-population sample of very preterm children at 6 years of age in southern Germany. The sample consisted of the following: 264 very preterm children (75.6% of German-speaking survivors); 264 term controls (matched for sex, socioeconomic status [SES], marital status and age of mother); and a representative normative sample for Bavaria (N=311). Compared with term peers, very preterm children scored significantly lower (approximately -1SD) on the measures of cognitive and language skills and had major cognitive deficits (<-2 SD) 10 to 35 times more often than the controls. Deficits in speech articulation and prereading skills (<l0th centile) were three to five times more frequent in very preterm children. More than 18% of very preterm children had cognitive deficits in more than five areas of functioning, compared with no control children. The differences between very preterm children and controls remained highly significant when only very preterm children (N= 229) and controls (N= 261) without major neurosensory impairment were considered. Little evidence for specific cognitive deficits was found once mental processing measured in the Kaufman Assessment Battery for Children (K-ABC) was controlled for. The effect of preterm birth on cognitive abilities was found to be larger than the influence of SES. In conclusion, there was a high prevalence of long-term multiple cognitive problems in very preterm children. These persistent cognitive problems appear to be of pre- or neonatal (treatment) rather than postnatal social origin.

Aptitude Tests↗

A randomized controlled trial comparing plasma removal with white cell reduction to prevent reactions to platelets.

BACKGROUND: Recent data suggest that most reactions to platelets are caused by white cell (WBC)-derived cytokines that accumulate in the plasma portion of the component during storage. On the basis of this theory, the effectiveness of two interventions to prevent reactions, poststorage WBC reduction and plasma depletion, were compared. STUDY DESIGN: A multiple crossover design was used, in which platelet components for transfusion to a patient randomly were WBC reduced after storage, or the plasma supernatant was removed. Adults >17 years of age, with a hematologic disease requiring platelet transfusion support, were eligible for the study. Patients were assessed for signs and symptoms characteristic of a reaction during, immediately after, and 1 hour after transfusion. Reactions were graded as mild, moderate, or severe. Interleukin 6 levels were also measured in the transfused platelet components. RESULTS: There were 380 analyzable platelet transfusions to 30 patients. The frequency of reactions was 25.8 percent (48/186) in the transfusions of poststorage WBC-reduced platelets and 17.0 percent (33/194) in the transfusions of plasma-depleted platelets (p<0.008). The severity of the reaction was graded by the patient. Severe reactions occurred more frequently in connection with poststorage WBC-reduced platelets than with plasma-depleted platelets: 33.4 percent (16/48) versus 18.2 percent (6/33), respectively (p = 0.048). Regression analysis identified interleukin 6 as the most significant of the evaluated factors in its correlation with the risk of reaction. CONCLUSION: Plasma removal is more effective than poststorage WBC reduction in preventing reactions, especially severe reactions to platelets.

Adolescent↗