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Biomedical subjects

M Luther

Publications and source records attributed to M Luther.

At least 73 records · Page 4Linked to original sources

Correlation of in vitro azole susceptibility with in vivo response in a murine model of cryptococcal meningitis.

Correlations between in vitro susceptibility and in vivo responses to fluconazole were sought in a mouse model of cryptococcal meningitis. Twenty clinical isolates were used. Two distinct populations were noted. Eight high-virulence isolates had an LD50 of < or = 252 cfu of Cryptococcus neoformans. Twelve low-virulence isolates had an LD50 of > 252 cfu. For 7 low-virulence isolates, the LD50 was > 20,000 cfu. C. neoformans also had a broad range of in vitro susceptibilities (MICs of 1.25 to > 80 micrograms/mL) at 24 h. A correlation was found between the MIC and the minimum effective dose of fluconazole in mice. This was observed with both survival and tissue counts as parameters of efficacy. This study documents for the first time the in vivo relevance of in vitro susceptibility to an azole antifungal for C. neoformans.

Acquired Immunodeficiency Syndrome↗

Pulsatile secretion of parathyroid hormone in normal young subjects: assessment by deconvolution analysis.

Preliminary reports suggest that PTH is secreted in a pulsatile fashion. However, available studies have not attempted to calculate actual PTH secretion rates in healthy individuals. To accurately characterize PTH secretory dynamics in healthy subjects, we studied seven young women and six young men, all of whom had hip and spine bone densities by dual photon densitometry in the upper tertile for age-matched control subjects. PTH concentrations were measured by immunoradiometric assay in blood sampled every 2 min over 6 h. Ionized calcium levels were obtained during the second and third hours of the study. Plasma PTH profiles were subjected to deconvolution analysis, which resolves measured hormone levels into secretion and clearance components. Cross-correlation analysis was performed to assess direct or inverse correlations between serum PTH and ionized calcium concentrations at various time lags. In these subjects, PTH was secreted in a dual fashion, with significant basal (tonic) secretion and PTH pulses approximately every 20 min. Pulsatile PTH secretion accounted for approximately 25% of the total secreted PTH. There were no differences in PTH secretory parameters between men and women, nor were there any significant correlations between PTH and ionized calcium concentrations. We conclude that in normal subjects, the predominant mode of PTH secretion is tonic, with superimposed PTH pulses of small amplitude but high frequency. The clinical significance of this complex physiological pattern of secretion awaits further study.

Adult↗

Treatment of peripheral vascular diseases--basic data from the nationwide vascular registry FINNVASC.

A national vascular registry, the FINNVASC registry, was introduced in Finland in the beginning of 1991. The registry covers the whole country--Finland has a population of 5.0 million habitants. During the first two years 8047 procedures were registered together with a 30-day follow-up. The number of surgical operations amounted to 5494 (68.3%), while the remaining 2553 procedures were endovascular. 22% of the surgical and 6.9% of the endovascular procedures were made as emergencies; about 10% of any procedure were reoperations. The indications for surgery were chronic limb ischaemia in 40.2% and acute limb ischaemia in 11.9%. Surgery of abdominal aortic aneurysm was indicated in 13.1% and surgical procedures in the aortocervical region in 13.3%. Access surgery was performed in 8.0% of the patients. Chronic limb ischaemia was the main indication, 92.1%, for the endovascular procedures, and renal artery stenosis was the second most frequent endovascular procedure, 2.7%. The mean length of hospital stay for surgical patients was 10.7 days and for patients treated with endovascular procedures 4.7 days. Patient outcome of 30 days of follow-up was comparable with the reports from other centres.

Adolescent↗

Effect of synchronous and asynchronous pulsatile flow during left, right, and biventricular bypass.

Ventricular assist devices augment flow from the left atrium to the aorta and/or from the right atrium to the pulmonary artery. Most devices are used in the asynchronous full-to-empty mode (asynchronous) but may also be used in a synchronous counterpulsation mode (synchronous). This study determines the optimal assist modes to reduce myocardial oxygen consumption (MVO2) and metabolism. Twelve pigs were instrumented with carotid artery and Baim coronary sinus catheters for determination of MVO2 and myocardial lactate production (LACT). Six were implanted with a Pierce-Donachy left ventricular assist device (LVAD) and 6 with both right and left ventricular assist devices (BIVAD). Two periods each of control, synchronous, and asynchronous bypass were instituted, the midanterior descending coronary artery (LAD) was ligated, and the sequence was repeated. After each period, MVO2 and LACT were determined and myocardial biopsy specimens were obtained for tissue, lactate, and ATP assay. Following LAD ligation, biopsy specimens were obtained from both the infarct and noninfarct zones of the heart. MVO2 decreased (p < 0.05) in the asynchronous BIVAD mode compared with control. MVO2 was unchanged in synchronous BIVAD or either LVAD mode. Tissue ATP and tissue lactate were unaffected by any mode of bypass. Only BIVAD in the asynchronous mode reduced MVO2. When ventricular assist devices are utilized to aid recovery of the natural heart, two devices should always be inserted to allow biventricular assist. Synchronous counterpulsation offers no advantage.

Adenosine Triphosphate↗

Growth hormone promotes early initiation of hepatocyte growth factor gene expression in the liver of hypophysectomized rats after partial hepatectomy.

GH accelerates hepatic regeneration in the rat. Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, is considered to be a major regulator of hepatic regeneration. In the present study, the effects of GH and insulin-like growth factor-I (IGF-I) on HGF gene expression in regenerating rat liver was investigated. In hypophysectomized rats treated with GH, hepatic HGF mRNA levels were increased 3 h after partial hepatectomy and reached peak levels after 5 h. In rats with intact pituitaries and in hypophysectomized rats not given GH treatment, HGF mRNA levels in liver were unchanged during the first 5 h following hepatectomy and reached peak levels after 10-18 h. DNA synthesis in the liver of GH-treated rats increased from low levels 10 h after hepatectomy to peak levels after 18 h. In rats without GH treatment the synthesis of DNA was still low 18 h after hepatectomy and was increased after 26 h. Treatment of hypophysectomized rats with IGF-I promoted increases in hepatic HGF mRNA levels and DNA synthesis 3.5 h and 15 h after hepatectomy respectively. HGF mRNA levels were constantly lower after sham-hepatectomy than after partial hepatectomy. In summary, in hypophysectomized rats the responses of hepatic HGF gene expression and DNA synthesis to partial hepatectomy were both accelerated by treatment with GH or IGF-I.

Animals↗

[24-hour blood pressure monitoring. Validation of a new automatic device].

To validate a new miniaturized 24-h blood pressure measuring device, 42 monitorings were carried out in 20 patients in the following manner: simultaneously with the automatic measurement, the physician involved measured the blood pressure in the usual manner with stethoscope and sphygmomanometer. The following very close agreement was found: Systolic: mean values 148 +/- 18/147 +/- 18 mmHg (Rxy = 0.98); diastolic: mean values 78 +/- 11/80 +/- 10 mmHg (Rxy = 0.96). These small differences show that, on account of its very high sensitivity, the Accutracker II recognizes the onset of the systolic k sound earlier on, and is capable of still detecting k sounds down to the lower diastolic pressures. These data, together with the good handling of the miniaturized device reveal it to be very well suited for the monitoring of anti-hypertensive treatment, thus helping to avoid unnecessary medication.

Blood Pressure Determination↗

Expression of the four subunits of the Torpedo californica nicotinic acetylcholine receptor in Saccharomyces cerevisiae.

Yeast expression vectors were constructed containing complementary DNA encoding the alpha-, beta-, gamma-, and delta-subunits of the Torpedo californica nicotinic acetylcholine receptor under the control of the Saccharomyces cerevisiae alcohol dehydrogenase promoter. All four plasmids were integrated into the yeast genome of a single yeast cell. The resulting yeast strain synthesized polypeptides novel to yeast that had the molecular weights and antigenic properties similar to the authentic T. californica receptor alpha-, gamma, and delta-subunits. The beta-subunit polypeptide could not be detected in this yeast strain, even though the poly(A)+ RNA from this strain contained all the information necessary for the expression of functional acetylcholine receptors in Xenopus laevis oocytes. The replacement of the beta-subunit mRNA 5'-untranslated leader and its N-terminal signal sequence by the corresponding alpha-subunit sequences, however, resulted in the expression of the beta-subunit polypeptide in yeast grown at 5 degrees C.

Animals↗

The human medulloblastoma cell line TE671 expresses a muscle-like acetylcholine receptor. Cloning of the alpha-subunit cDNA.

Nicotinic acetylcholine receptors (AChRs) from muscle bind alpha-bungarotoxin (alpha Bgt) and are composed of four kinds of subunits, whereas AChRs from mammalian brains do not bind alpha Bgt and are composed of two kinds of subunits. alpha Bgt-binding proteins whose function is unknown are also found in brain. All these proteins belong to the same gene family. The human medulloblastoma cell line TE671 expresses a functional AChR which binds alpha Bgt. Surprisingly, the AChR of this neuron-derived cell line has electrophysiological, immunological and biochemical properties different from neuronal AChRs and very similar to muscle AChRs. The TE671 AChR binds alpha Bgt, but is different from alpha Bgt-binding proteins in brain. Here we show that TE671 expresses the alpha-subunit mRNA coding for the muscle AChR, thereby proving that TE671 expresses a muscle-type AChR that is not expressed in adult brain. The isolated cDNA clones should prove useful for expression of large amounts of human muscle-type AChR alpha-subunit protein for studies of the autoimmune response to muscle AChRs in human myasthenia gravis.

Amino Acid Sequence↗

[Long-term artificial respiration at home in restrictive ventilation disorders].

Combined chest wall and lung alterations may lead to severe restrictive respiratory disorder. In advanced cases with hypercapnia, hypoxemia and oxygen intolerance during spontaneous breathing, there are almost insuperable therapeutic difficulties. Three of such patients have been treated, after tracheostomy, at home for 60, 34 and 22 months respectively by intermittent IPPV ventilation. With an improved quality of life all these patients survived up to now. This result seems to be encouraging.

Activities of Daily Living↗

[Papillary fibroelastoma of the aortic valve. Sudden death caused by an uncommon tumor of the heart].

We describe a very rare tumor of the heart with a pendulous papillary fibroelastoma of the aortic valve, obstructing the ostium of the LCA - resulting in the sudden death of a healthy 40-year-old man. Acute severe ischemia was registered in the ECG a few minutes before death - corresponding especially to the myocardial regions perfused by the LCA. There is no doubt from the post mortem findings that the sudden death of this patient was caused by occlusion of the left coronary ostium by the pendulous papillary fibroelastoma.

Adult↗

[Global and regional left ventricular myocardial function following aorto-coronary multiple (5-, 6-, 7-) bypass. Non-invasive determination with technetium 99m-pertechnetate scintigraphy].

In 19 patients (mean age 55.3 years) with severe, diffuse coronary artery disease and stable angina pectoris, coronary artery bypass surgery was performed with an average of 5.36 anastomoses per patient. At 15.5 +/- 8 months postoperatively, radionuclide ventriculograms were obtained in the RAO projection (first-pass-technique) at rest and during maximal exercise by means of a multicrystal camera. To assess the effects of revascularization on the myocardial function, analysis was performed for global ejection fraction (GEF) as well as three regional ejection fraction (GEF) as well as three regional ejection fractions (REF) corresponding to the vascular beds of the three major coronary arteries. During exercise global ejection fraction increased in 13 patients (68.4%) an average of 9.5%-points from 51.5 to 61.0%, in one patient (5.2%) remained unchanged and in five patients (26.3%) decreased an average of 9.6% %-points from 62.6 to 53.0% (all changes p less than 0.05). The classification of the various myocardial regions was based on the preoperative coronary angiogram as well as intraoperative in-situ findings according to the status of the coronary vessels, the extent of revascularization and the presence of remote myocardial infarctions. Regions of group I had a significantly higher fraction of complete revascularizations, that is 79.9%. 61.1% of group-II-territories were incompletely revascularized. The weighted balance of the three regions supplied by the left anterior descending artery, the circumflex and the right coronary artery explains the postoperative response of the global ejection fraction to exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

[Clinical significance of aberrant coronary artery--origin from the aorta (author's transl)].

It is demonstrated the unusual case of a 14-year-old boy, dying suddenly after physical stress with myocardial infarction. Autoptically it was found a coronary artery anomaly of the "malign type" and in addition a significant narrowing of the left main coronary artery. There are presented until now in the literature 17 cases of sudden death in young patients (up to 22 years) in connection with the "malign coronary artery anomaly origin" of both coronary arteries from the right coronary sinus and course of the left coronary artery between the truncus of pulmonary artery and aorta. All 17 cases of sudden death were male. No explanation of the predominance of the male sex is known. Always physical stress preceded the fatal event. Obviously all other abnormalities of coronary artery origin of the aorta and course--except the Bland-White-Garland Syndrome--are of minor clinical importance. In the course of life all coronary vessel anomalies can be accompanied by atherosclerotic processes, followed by clinical symptoms of coronary artery disease. The additional speciality of the demonstrated case is the significant stenosis (75%) in the abnormal course of the main coronary artery. Practical consequence of the presented case is: Even in young patients and children one must be aware of the possibility of a myocardial infarction with coronary artery abnormality if clinical symptoms are present. There may be diagnostic (coronary arteriography) and therapeutic (coronary artery surgery) consequences, if the patient survives the life-threatening event.

Adolescent↗

[Cardiogenic shock following acute myocardial infarction. Pathophysiology and clinical aspects (author's transl)].

The starting point of cardiogenic shock is an extensive myocardial infarction. Through a backward and forward failure of the left ventricle a shock-specific disturbance of the microcirculation occurs with a reduction of the circulation in the periphery of the body and development of a tissue acidosis (metabolic acidosis). Fall in blood pressure and cardiac volume, congestion of blood in the region of the pulmonary vessels and signs of reduced circulation in the body periphery (severe physical weakness, apathy, cold and clammy skin, oliguria) determine the clinical picture of cardiogenic shock. Therapeutically, intra-aortal balloon counter-pulsation, possibly combined with a cardiosurgical intervention, has reduced the mortality of cardiogenic shock after acute myocardial infarction from 90--100% to 60--70%.

Acute Disease↗