Optical phonons in YBa2Cu4O8 and Y2Ba4Cu7O15- delta.
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Biomedical subjects
Publications and source records attributed to R Kremer.
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We have examined circulating concentrations of a parathyroid hormone-like peptide (PLP) in patients with malignancies and in patients with hyperparathyroidism. The radioimmunoassay employed reacts with synthetic amino-terminal fragments of PLP but not with parathyroid hormone. Elevated plasma PLP concentrations were observed in 50% of patients with malignancy and hypercalcemia and in 15% of normocalcemic cancer patients, mean values being higher in the former group. Detectable plasma PLP concentrations were found in 2 of 39 control subjects. In 2 patients with breast cancer plasma PLP declined concomitantly with a reduction in tumor burden. Adenocarcinoma of the breast and squamous cell carcinomas were most frequently associated with high plasma PLP levels although a variety of histologic types were represented. The presence of metastases on bone scans did not correlate with either the severity of hypercalcemia or the extent of PLP elevation. Increased concentrations of plasma PLP were also observed in 4 of 20 patients with primary hyperparathyroidism and in 5 of 16 patients with chronic renal failure and secondary hyperparathyroidism. Gel filtration analysis of immunoreactive PLP in plasma from 2 hypercalcemic breast cancer patients revealed heterogeneity, with, in each case, both large (greater than 15 kD) and small (6-7 kD) molecular weight amino-terminal moieties. The results document the presence of PLP in the circulation of patients with cancer and are consistent with a pathogenetic role for PLP in the hypercalcemia of malignancy irrespective of whether skeletal metastases have occurred. PLP may also contribute to the skeletal and/or renal manifestations of hyperparathyroid states.
Doxorubicin (Adriamycin) is an effective anticancer agent but its therapeutic value is limited by its myocardial cardiotoxicity. To improve early detection of doxorubicin cardiotoxicity, studies were performed in patients with long-term doxorubicin treatment using pulsed Doppler echocardiography to assess the changes in left ventricular (LV) diastolic filling dynamics. M-mode echocardiographic systolic parameters and Doppler transmitral flow velocities were analyzed in two groups of patients. In group A (45 patients, mean age 45 +/- 13 years), the results were compared with those of a control group of 35 normal subjects matched for age. In group B (19 patients, mean age 44 +/- 12 years), the pretreatment results were prospectively compared with those obtained during treatment protocol. The patients received a cumulative dosage of 253 +/- 125 mg/m2 of doxorubicin for group A and 240 +/- 135 mg/m2 for group B. After doxorubicin treatment, in the two groups there were no significant changes in LV dimensions, shortening fraction, and mean velocity of circumferential fiber shortening (VCF). In contrast, Doppler echocardiographic parameters of diastolic function were significantly modified after doxorubicin in the two groups:isovolumic relaxation period was prolonged by 32% in group A (p less than 0.001) and by 22% in group B (p less than 0.005).2+ The early peak flow velocity was reduced by 18% in group A (p less 0.002) and by 13% in group B (p less than 0.04), and the ratio early peak flow velocity/atrial peak flow velocity also decreased significantly, by 23% in group A (p less than 0.001) and by 20% in group B (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
A 43-year-old woman had clinical and biochemical evidence of a secreting paraganglioma of the glomus jugulare region. Catecholamine secretion was exacerbated during embolization of the tumor before surgery and resulted in a life-threatening vasomotor attack. Preoperatively, pharmacologic blockade of excessive catecholamine secretion with prazocin controlled her blood pressure, tachycardia, and symptoms. The tumor was resected and its catecholamine content measured. This case is reported to stress the importance of adequate preoperative assessment of patients with paragangliomas of the head and neck. The extreme rarity of catecholamine-secreting tumors of this region should not lead us to underestimate the morbidity and mortality of such patients undergoing surgery or any other invasive procedure whether the diagnosis is confirmed or only suspected.
Exposure of quiescent bovine parathyroid cells to serum or a serum substitute caused an elevation in [3H] thymidine incorporation, followed by an increase in cell number. This was preceded by a rapid transient rise in c-myc and c-fos proto-oncogene mRNA levels. Alterations in the medium calcium concentration had no effect on the growth state of quiescent parathyroid cells. In addition, varying the medium calcium concentration did not influence either the time course or the degree of induction of proto-oncogene expression or the subsequent increase in [3H] thymidine uptake or proliferation of stimulated parathyroid cells. In contrast, when 1,25-dihydroxycholecalciferol was added with serum or serum substitute to quiescent parathyroid cells, no increase in c-myc mRNA levels was observed, and the expected increase in parathyroid cell number failed to occur. The augmentation in c-fos mRNA in response to serum was not, however, altered by 1,25-dihydroxycholecalciferol. These results indicate that 1,25-dihydroxyvitamin D, but not extracellular calcium, may directly modulate parathyroid cell proliferation by altering the expression of specific replication-associated oncogenes.
Ergonovine testing was performed in 40 patients with normal coronary angiograms (24 men, 16 women, mean age 53 years) complaining of chest pain. Esophageal and coronary spasm were assessed by simultaneous esophageal manometry, 12-lead-EKG and myocardial scintigraphy. Progressive doses of ergonovine were injected. Of the 17 patients experiencing chest pain during testing, coronary spasm occurred in 3 and esophageal motor disorders in 7 (peristaltic contraction waves of high amplitude in 3, diffuse esophageal spasm in 4). The dose necessary was more than 0.175 mg. No objective changes (EKG and manometry) were observed in the 7 remaining patients.
Magnetic resonance imaging is being used increasingly to provide information unobtainable by other imaging techniques. Clinicians have been reluctant to use this technique on patients who have had a stapedectomy because the prosthesis is composed of metal and may move in the electromagnetic fields. We investigated the materials used with respect to their ability to become magnetized and the forces acting on them in a static electromagnetic field, using the SQUID technique. We concluded that there is no danger of a metallic stapedectomy prosthesis becoming displaced by the magnet of a 1.0 or 1.5 T magnetic resonance imaging unit.
It has been previously shown that undercomplaining behaviour is involved in the 'silence' of Silent Myocardial Ischaemia (SMI). By means of symptom checklists completed blindly by both the patient and his spouse we found that: (1a) at an individual level, even in non-cardiac related symptoms areas (everyday illnesses), SMI patients have a lower propensity to complain than symptomatic patients; yet (1b) they describe the same level of worrying about symptoms as painful patients. (2) At a second level, when looking at patient-spouse discrepancies it appears that the spouse of the SMI patient describes the patient as having not only more symptoms but also as being less worried than he reports. On the contrary, the spouse of the symptomatic patient generally describes the patient as having fewer symptoms than he does and as being more worried by the symptom's appearance than he reports. These data support the denial hypothesis in SMI and allow us to consider the spouse not only as a good anamnestic collaborator in order to avoid information biases in SMI but also as a potential warning system that could be used in prevention and treatment strategies related to SMI.
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Thirty-six patients with chronic obstructive pulmonary disease (COPD) were studied by pulsed Doppler echocardiography. In 32 of the 36 patients, adequate Doppler signals were obtained in the pulmonary arterial trunk and correlated with right cardiac hemodynamics. The studied group included 26 patients with mean pulmonary arterial pressure (MPAP) greater than 20 mm Hg at rest (group A, with pulmonary hypertension) and six patients with MPAP of 20 mm Hg or less (group B, without pulmonary hypertension). A control group (group C) consisted of 12 subjects with normal hemodynamic data and pulmonary function. Analysis of Doppler data included flow velocity curve pattern, presence of a negative presystolic velocity, right ventricular pre-ejection period (RVPEP) and ejection period (RVEP), time between onset and peak of pulmonary velocity (time to peak velocity, TPV) and derived ratios of TPV/RVPEP and TPV/RVEP. In patients with pulmonary hypertension, the Doppler flow velocity curve in the pulmonary trunk showed a rapid acceleration and an early deceleration. The mean value for TPV was 78 +/- 12 msec in group A, 115 +/- 11 msec in group B, and 127 +/- 10 msec in group C. In patients with COPD, significant correlations were observed between TPV and log10 MPAP (r = -0.77; SEE = 0.07) and between TPV and log10 total pulmonary resistances (r = -0.84; SEE = 0.05). Accordingly, pulsed Doppler echocardiography may be a useful tool to predict pulmonary hypertension due to chronic pulmonary disease.
Between April, 1977, and November 1984, 136 porcine bioprosthetic valves were implanted in 122 patients principally selected on the basis of age and contraindication to anticoagulants. The following procedures were carried out: aortic valve replacement (AVR) 88, pulmonary valve replacement (PVR) 1, mitral valve replacement (MVR) 38, and tricuspid valve replacement (TVR) 9. The ages ranged from 25 to 84 years (mean 64.6 years). The 30-day mortality was 11.5% overall. Survivors were followed up to 7 years (mean 29.2 months). Actuarial survival rates at 5 years, including operative deaths, were as follows: AVR 76.2 +/- 9.3%, MVR 59.7 +/- 12.6% and combined valve replacement (CVR) 47.1 +/- 19.4%. The 5-year probability of freedom from valve-related complications was 76.8 +/- 6.9% for all patients. The rate of thromboembolic events was 3.80% per patient-year after AVR and 2.72% per patient-year after MVR and CVR. The embolic rate did not differ between patients treated with anticoagulants and those treated with platelet antiaggregators. Primary tissue valve failure occurred in 2 patients for a linear incidence of 0.77% per patient-year. Postoperative echocardiography was performed in 83% of the survivors. Patients are now prospectively followed up by bidimensional echography and pulsed Doppler in order to detect early valvular dysfunction. The performance of the Carpentier-Edwards porcine bioprosthesis is, thus, satisfactory in this group of elderly patients.
We have purified peptides with PTH-like bioactivity from a rat Leydig cell tumor (H-500) and a human squamous cell carcinoma, both associated with a syndrome of humor-induced hypercalcemia. Tumor extracts were shown to be active in an in vitro renal cytochemical bioassay and in an in vitro osteosarcoma cell (UMR 108) adenylate cyclase assay; activity in both assays could be reduced by the PTH antagonist [norleucine-8,18,tyrosine-34]bovine PTH-(3-34)-amide. Partially purified extracts of both tumors and of rat tumor-conditioned culture medium were active in vivo in thyroparathyroidectomized rats in preventing hypocalcemia and increasing fractional phosphorus excretion and cAMP excretion. Ion exchange chromatography demonstrated that active peptides were basic in character. Employing reverse phase HPLC and gel permeation HPLC, active peptides of approximately 9,000 and 9,500 daltons were purified from extracts of the human and rat tumors, respectively, which had similar but not identical compositions. Two additional bioactive peptides were detected in rat tumor extract, and the more active had a mol wt of approximately 28,000. The results demonstrate that peptides that mimic PTH in a variety of in vivo and in vitro bioassays can be extracted from malignancies associated with hypercalcemia, that multiple molecular species may be detected in tumors that demonstrate PTH-like activity, and that at least one of these peptides may be similar in two tumors of highly divergent cell and species origin.
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Bacterial endocarditis still remains a serious disease with significant morbidity and mortality. In patients with known valve disease, most cases are caused by oral viridans streptococci. These organisms are present in vast numbers on the gum margins and in gum pockets. They cause transient bacteraemia during eating and tooth brushing. More substantial, but short-lived bacteraemia can occur during dental treatment such as extraction and scaling. Bacteria may then become attached to abnormal endocardium leading to the development of infective endocarditis. Prophylaxis of endocarditis during dental procedures in patients with known valve disease should thus be aimed at reducing the number of bacteria entering the blood stream and eliminating those that get there. This can be sought first by good oro-dental hygiene and secondly by the use of prophylactic antibiotics. In this paper, we set out simple guidelines for practitioners in those countries that do not already have recommendations of their own. They are based on guidelines already in use in the United Kingdom, France, Switzerland and the United States.
Ventricular septal wall motion, assessed by M-mode echocardiography, was analyzed, retrospectively, in 324 patients after open heart surgery (214 patients with valvular replacement, 110 patients with aorto-coronary bypass surgery); the mean follow-up was 14 months (1 month to 5 years). In the early (less than 1 month) postoperative period, an anterior systolic (paradoxical) motion of septum (PVSM) was observed in 66% of the patients with valvular surgery, and in 76% of those with coronary surgery. PVSM disappears progressively: one year after surgery, it occurs in only 21% of patients with valvular surgery and in 16% of patients with coronary surgery. There is no significant difference in frequency and evolution of PVSM between the different types of surgical interventions (valvular versus coronary surgery; aortic versus mitral surgery; single bypass graft versus multiple bypass grafts). The similar frequency and evolution of PVSM after aorto-coronary venous graft surgery and valvular replacement surgery support the hypothesis that PVSM would be the expression of a greater anterior systolic motion of the whole heart, related to the loss of pericardial restraint. PVSM disappears slowly after surgery, probably following the development of cardiothoracic adherences.
Human and bovine parathyroid gland slices were incubated in vitro for varying time periods with inorganic 32P and [35S]methionine or [3H]serine. Tissue was then extracted with aqueous medium, and parathyroid hormone (PTH) purified. Incorporated 32P was found to coelute with immunoreactive PTH in multiple chromatographic systems, and a peak of phosphorylated material could be resolved from the nonphosphorylated hormone by reversed phase high pressure liquid chromatography. The amino acid composition of both the phosphorylated and the nonphosphorylated entities conformed to that of the major glandular species of PTH, and phosphorylated hormone accounted for 10-20% of the total. A time course revealed slow incorporation of 32P into hormone, and after a 4-h preincubation with inorganic 32P, co-elution of 32P with both PTH and its precursor was observed. Phosphoserine was identified in purified PTH labeled with [3H]serine. Additionally dilute acid hydrolysis of PTH, labeled with [35S]methionine and containing 32P, generated an 35S-labeled fragment with which 32P co-chromatographed. The results are consistent with in vitro phosphorylation of PTH on serine residues within the NH2-terminal region of the hormone by both human and bovine glands and suggest that phosphorylation of the prohormone occurs as well.