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Biomedical subjects

K Strasser

Publications and source records attributed to K Strasser.

At least 19 recordsLinked to original sources

Prospore membrane formation linked to the leading edge protein (LEP) coat assembly.

In yeast, the differentiation process at the end of meiosis generates four daughter cells inside the boundaries of the mother cell. A meiosis-specific plaque (MP) at the spindle pole bodies (SPBs) serves as the starting site for the formation of the prospore membranes (PSMs) that are destined to encapsulate the post-meiotic nuclei. Here we report the identification of Ady3p and Ssp1p, which are functional components of the leading edge protein (LEP) coat, that covers the ring-shaped opening of the PSMs. Ssp1p is required for the assembly of the LEP coat, which consists of at least three proteins (Ssp1p, Ady3p and Don1p). The assembly of the LEP coat starts with the formation of cytosolic precursors, which then bind in an Ady3p-dependent manner to the SPBs. Subsequent processes at the SPBs leading to functional LEP coats require Ssp1p and the MP components. During growth of the PSMs, the LEP coat functions in formation of the cup-shaped membrane structure that is indispensable for the regulated cellularization of the cytoplasm around the post-meiotic nuclei.

Fluorescent Antibody Technique↗

Changes in lung parenchyma after acute respiratory distress syndrome (ARDS): assessment with high-resolution computed tomography.

The aim of this study was to evaluate the appearance, extent, and distribution of parenchymal changes in the lung after acute respiratory distress syndrome (ARDS) as a function of disease severity and therapeutic procedures. High-resolution computed tomography (HRCT), clinical examination, and lung function tests were performed in 15 patients, 6-10 months after ARDS. The appearance and extent of parenchymal changes were compared with the severity of ARDS, as well as with clinical and therapeutic data. Lung parenchymal changes resembling those found in the presence of pulmonary fibrosis were observed in 13 of 15 patients (87%). The changes were significantly more frequent and more pronounced in the ventral than in the dorsal portions of the lung ( p<0.01). A significant correlation was observed between the extent of lung alterations and the severity of ARDS ( p<0.01), and the duration in which patients had received mechanical ventilation either with a peak inspiratory pressure greater than 30 mmHg ( p<0.05), or with more than 70% oxygen ( p<0.01). Acute respiratory distress syndrome frequently is followed by fibrotic changes in lung parenchyma. The predominantly ventral distribution of these changes indicates that they may be caused by the ventilation regimen and the oxygen therapy rather than by the ARDS.

Adolescent↗

Aromatase inhibitors in the treatment and prevention of breast cancer.

PURPOSE: The purpose of this article is to provide an overview of the current clinical status and possible future applications of aromatase inhibitors in breast cancer. METHODS: A review of the literature on the third-generation aromatase inhibitors was conducted. Some data that have been presented but not published are included. In addition, the designs of ongoing trials with aromatase inhibitors are outlined and the implications of possible results discussed. RESULTS: All of the third-generation oral aromatase inhibitors--letrozole, anastrozole, and vorozole (nonsteroidal, type II) and exemestane (steroidal, type I)--have now been tested in phase III trials as second-line treatment of postmenopausal hormone-dependent breast cancer. They have shown clear superiority compared with the conventional therapies and are therefore considered established second-line hormonal agents. Currently, they are being tested as first-line therapy in the metastatic, adjuvant, and neoadjuvant settings. Preliminary results suggest that the inhibitors might displace tamoxifen as first-line treatment, but further studies are needed to determine this. CONCLUSION: The role of aromatase inhibitors in premenopausal breast cancer and in combination with chemotherapy and other anticancer treatments are areas of future exploration. The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.

Anticarcinogenic Agents↗

Symptomatology of anemia.

The symptoms and severity of anemia depend on various factors, including the degree of anemia, the rapidity of its onset, and the age and physiologic status of the patient. Although the human body tries to counterbalance the effects of anemia by various mechanisms, almost every organ system of the human body is eventually affected. The symptoms experienced by patients vary from cold skin, dizziness, and palpitations to pulmonary edema, heart failure, depression, and severe impairment of cognitive function. Anemia substantially impacts patients' quality of life, a fact that has been shown in several clinical trials in patients with renal disease as well as in patients suffering from various malignancies undergoing chemotherapy. These studies evaluated the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) to anemic patients, and it was shown that raising hemoglobin levels with epoetin alfa ameliorated the symptoms of anemia and significantly improved the functional status and overall quality of life in cancer patients. Furthermore, preliminary data indicate that the correction of anemia in cancer patients may in addition improve treatment efficacy and possibly overall survival.

Anemia↗

Chemoprevention with aromatase inhibitors--trial strategies.

Estrogen and its catechol metabolites from both the circulation and synthesized within the breast are important in the pathogenesis of breast cancer. Blocking estrogen's effects on the breast with selective estrogen receptor modulators (SERMS) is an ongoing strategy. Thus, tamoxifen and raloxifene reduce risk as monotherapy. Aromatase (estrogen synthetase) inhibitors are a logical alternative to SERMS. To date, SERMS have demonstrated reduction only in estrogen-progesterone receptor positive cancers without reduction in receptor negative tumors. By inhibiting the parent estrogens and their catechol metabolites, true prevention of cancer initiation might occur and reduction not only in the receptor positive but also negative tumors might result. Ongoing adjuvant breast cancer trials are exploring aromatase inhibitors as alternatives to tamoxifen, or in sequence or in combination with tamoxifen. Relative efficacies including reduction in contralateral breast cancer, toxicities and end-organ effects and impact on quality of life, are being explored. Data from these trials will help to guide future chemoprevention strategies. Proof of principal trials in 'high risk' cohorts such as premalignant breast lesions, dense screening mammograms, high plasma estradiol levels or increased bone density are already ongoing. Issues such as dose, schedule, therapeutic index and mono versus combination therapy are important to define.

Animals↗

Role of the spindle pole body of yeast in mediating assembly of the prospore membrane during meiosis.

Spindle pole bodies (SPBs) are the centrosome equivalents in yeast, required for microtubule organization. In yeast, the SPB further serves as the attachment sites of the prospore membrane during meiosis. Here we report the identification of two new meiosis-specific components of the SPB, Mpc54p and Mpc70p, and the first protein specific for the prospore membrane, Don1p. Mpc54p and Mpc70p are not present in mitotic SPBs, and during meiosis II they are components of a meiosis-specific structural alteration of the outer plaque of the SPB. Both proteins are dispensable for the meiotic divisions but are essentially required for the formation of the prospore membrane. In the mpc54 and mpc70 mutants, the Don1p-containing precursors of the prospore membrane can still be found in the cytoplasm and associated with the SPB. Unexpectedly, however, the assembly of the precursors to a continuous membrane system is affected. Thus, the meiotic SPB is directly involved in the formation of a specialized membrane system, the membrane of the prospore.

Amino Acid Sequence↗

Liarozole fumarate (R85246): in the treatment of ER negative, tamoxifen refractory or chemotherapy resistant postmenopausal metastatic breast cancer.

Three phase II studies were conducted to determine the efficacy and tolerability of liarozole fumarate (R85246; liarozole), a retinoic acid metabolism blocking agent (RAMBA) and aromatase inhibitor. Additionally, animal experiments in the MNU-induced rat mammary tumor model and in immature ovariectomized rats were conducted to further elucidate liarozole's mechanisms of action. Patients were postmenopausal with either: ER negative disease in first relapse (Group 1: 1n = 16); ER positive or unknown disease refractory to tamoxifen (Group 2; n = 16); ER positive, negative or unknown disease resistant or refractory to chemotherapy (Group 3; n = 27). Treatment was liarozole (150-300mg) twice daily orally until disease progression. Response rates were: 25% in group 1 (95% CI 11.0-52.3%: median duration (MD) 20 months; range 2-36.5); 25% in group 2 (95% CI 11.0-52.3%; MD 6.5 months: range 3.5-38): 11% in group 3 (95% CI 4.2-29.2%; MD 7 months; range 3-8.5). No significant improvement in quality of life scores (FLI-C) was noted. Toxicities observed were predominantly dermatological (skin disorders: 88%; dry mouth/eyes/lips: 69%). Plasma estradiol decreased from mean pre-treatment levels of 72.7 pM (9.1-1,839 pM) to below detection (9.2 pM) after 1 month. Liarozole, but not vorozole, partially inhibited estradiol induced uterine hypertrophy and demonstrated dose-dependent anti-tumor effects in the rats, only partially overcome by coadministration of estradiol. The clinical responses observed, together with our preclinical results, confirm liarozole's dual mechanism of action and provide a rationale for further evaluation of RAMBAs in the treatment of breast cancer.

Administration, Oral↗

Effects of rocuronium and vecuronium on intracranial pressure, mean arterial pressure and heart rate in neurosurgical patients.

We have evaluated the effects of a single bolus dose of rocuronium 0.6 mg kg-1 (group 1, n = 10) or vecuronium 0.1 mg kg-1 (group 2, n = 10) on intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and heart rate (HR) in 20 neurosurgical patients undergoing mechanical ventilation of the lungs during continuous sedation with sufentanil and midazolam. Before and after neuromuscular block using twice the ED90 of the blockers, ICP, MAP, CPP and HR were recorded continuously for 15 min. Treatment caused no significant changes in ICP, CPP or MAP and there was no evidence of histamine release. Mean maximum block in the rocuronium group was slightly less than that in the vecuronium group (95.9 (3.1)% vs 100%; ns) The difference between the two groups in onset time (rocuronium 142 (62) s, vecuronium 192 (64) s; P = 0.04) was significant. Patients in the rocuronium group showed a slight (7(4)%) but significant (P = 0.003) increase in heart rate.

Adult↗

[Jet ventilation superimposed on a special jet laryngoscope for endoluminal stent insertion in the tracheobronchial system].

BACKGROUND: Stenotic processes of the tracheobronchial system may lead to dyspnoea that can become lift-threatening. To restore sufficient function of the blocked airway, a silicone stent can be inserted. The anaesthesia techniques used for this intervention so far have been complicated. The object of this study was to determine whether the super-imposed high-frequency jet ventilation (SHFJV) via the jet laryngoscope originally designed for microlaryngeal surgery can be utilized for endoluminal stent insertion. METHODS: In 12 patients with acute respiratory insufficiency (ASA 3-5) due to stenosis of the tracheobronchial system, an endoluminal silicone stent was inserted through the jet laryngoscope while the patient was ventilated using SHFJV: RESULTS: A significant rise in paO2 readings prior to the jet ventilation and subsequent measurements was observed. The CO2 elimination was good (average paCO2 31.5 +/- 7.5-53.1 +/- 14 mmHg). Variably high paCO2 readings during stent insertion were related to the respective surgical phases. At the end of the surgical manipulation, all patients had sufficient spontaneous ventilation. CONCLUSIONS: First clinical applications of the jet laryngoscope combined with superimposed jet ventilation for stent insertion demonstrated satisfactory results. Not only were the patients ventilated throughout the procedure, but CO2 elimination was also satisfactory. Superimposed jet ventilation provides a sufficient tidal volume with low ventilation pressures, and therefore oxygenation and CO2 elimination are unproblematic. SHFJV enables the anaesthetist to ventilate the patient nearly continuously with minimal phases of apnoea. The only apnoea phases, as with any other method, occur during surgical manipulation while inserting the stent and thus blocking the airway. We believe that the jet laryngoscope with SHFJV presents a distinct advantage for both anaesthetist and surgeon when inserting stents in the tracheobronchial system.

Acute Disease↗

Spontaneous pneumocephalus in a newborn infant with myelomeningocele and hydromyelia.

The authors report a preterm boy, born at 35 weeks gestation with hydrocephalus and an open sacral myelomeningocele. Cranial ultrasound showed ventricular dilatation with posture-dependent intraventricular bright echoes, representing air. Ultrasound of the cervical spine and the craniocervical junction revealed marked hydromyelia of the whole spinal cord, as well as a Chiari II malformation. Air penetrating the enlarged central canal through the neural tube defect and subsequently ascending to the cranial cavity was demonstrated by fluoroscopy. After a review of the literature, the authors conclude that the association of spontaneous pneumocephalus with myelomeningocele could indicate severe hydromyelia. These malformations are readily demonstrated by ultrasound in newborn infants.

Humans↗

[Giant cystosarcoma phylloides: mammographic and sonographic findings in an unusual case].

Cystosarcoma phylloides (also called phylloides tumour) is a rare fibroepithelial mixed tumour which accounts for 0.3 to 1% of all breast neoplasms. Diagnosis can be strongly suspected after clinical, mammographical and especially sonographical findings. Neither mammography nor sonography and even not aspiration cytology can be reliably used to differentiate between benign and malignant tumours. In the following a patient is presented in whom cystosarcoma phylloides attained, even for this kind of tumour, an unusually large dimension.

Breast Neoplasms↗

[The radiological diagnosis of the male breast. Mammography, sonography and pathohistological correlation].

61 men with breast enlargement underwent mammography; complementary sonography was performed in 34 cases. Diagnoses included gynaecomastia in 53 cases, pseudo-gynaecomastia in 9 cases, 3 carcinomas, 2 inflammatory lesions and 1 lipoma. Gynaecomastias of up to four month's duration are histologically of the florid type and show a nodular or nodular-dendritic mammographic pattern; sonography usually demonstrates a focal hypo-echogenic area. Gynaecomastias of longer duration representing the fibrous type show mammographically a dendritic or diffuse pattern and sonographically a hyper-reflexive breast parenchyma. Mammography and sonography can differentiate reliably true gynaecomastia from pseudo-gynaecomastia. Gynaecomastia and especially inflammatory lesions may not always be readily differentiated from carcinoma. Sonography can be helpful by demonstrating hyper-reflexive glandular tissue, whereas carcinomas are usually hypoechoic.

Adolescent↗

Phylloides tumor: findings on mammography, sonography, and aspiration cytology in 10 cases.

Phylloides tumor is a rare fibroepithelial breast tumor that occasionally has unpredictable clinical behavior. In nine cases of histologically benign tumors and one case of malignant phylloides tumor, the findings on physical examination, mammography, sonography, and aspiration biopsy were correlated retrospectively with the histologic diagnosis of resected specimens. Mammograms showed a round or lobulated benign-appearing opacity in nine cases; one small tumor was missed mammographically. Sonography depicted all tumors as mostly solid masses. Sonographic features included low-level internal echoes, either uniform or scattered; smooth contours; and no significant posterior shadowing. Intramural cysts were shown in six cases. Neither mammography nor sonography allowed reliable differentiation between benign and malignant phylloides tumors. Aspiration biopsy permitted accurate diagnosis of seven benign tumors. The malignant phylloides tumor was classified as a malignant tumor, but the definite differentiation from a carcinoma could not be made. Two histologically benign phylloides tumors were misdiagnosed as carcinomas. Although uncommon, phylloides tumor should be considered in the differential diagnosis of mammographically benign-appearing breast masses, especially if sonography shows intramural cysts within a well-defined solid lesion. Aspiration cytology is unreliable because of the inhomogeneity of the tumor; both intraoperative frozen section and permanent sections are needed for correct histologic diagnosis.

Adult↗

High-resolution ultrasonography of the carpal tunnel.

Twenty-eight wrists of 25 patients with carpal tunnel syndrome (CTS) and 28 wrists of 14 normal control subjects were studied with high-frequency real-time ultrasonography. Three general findings could be observed in CTS, regardless of its cause: swelling of the median nerve at the entrance of the carpal tunnel; flattening of the median nerve in the distal carpal tunnel; and increased palmar flexion of the transverse carpal ligament. Quantitative analysis proved these findings to be significant. We conclude that high-resolution sonography is able to diagnose median nerve compression in the carpal tunnel syndrome and to detect some of its potential causes.

Adult↗

[Continuous spinal anesthesia versus continuous epidural anesthesia in surgery of the lower extremities. A prospective randomized study].

Continuous epidural anesthesia (CEA) is generally accepted as a routine method of regional anesthesia while there has been only limited application of continuous spinal anesthesia (CSA), due mainly to a lack of adequate spinal catheters. With the introduction of a new, ultra-thin spinal catheter (32 G) inserted via a thin puncture needle, some of the complications reported after CSA can be eliminated. We studied CSA versus CEA in lower-extremity operations. METHODS. We evaluated 33 patients in a prospective, randomized study. All were comparable with respect to age, anesthetic risk (ASA II-III), and pre-existing diseases. The only exclusion criterium was the presence of a coagulation disturbance. The CSA group consisted of 17 patients (mean age 75.5 +/- 0.1 year); 26 G puncture needle and 32 G catheter were used. The CEA group consisted of 16 patients (mean age 73.8 +/- 11.0 years); an 18 G puncture needle and 22 G epidural catheter with a stylet were inserted with the loss-of-resistance technique. Both catheters were placed with the patient in a sitting position and left in place for 24 h in order to administer local anesthetics (LA) for postoperative analgesia as required. Hemodynamic parameters-mean arterial pressure (MAP) and heart rate (HR)-were compared in each group at 5-min intervals for 30 min after administration of local anesthetic and at 10-min intervals during the operation. Additionally, the ECG, pulse oximetry, respiratory rate, diuresis, and blood gases were monitored. After placement of the catheter, patients in the CSA group received 1.9 ml (+/- 0.2) bupivacaine HCl 0.5%. Patients in the CEA group received 12.6 ml (+/- 2.5) bupivacaine HCl 0.5%. For statistical evaluation of the data we used mean values, standard deviation (+/-), the Kruscal-Wallis procedure, and Student's t-test for unpaired data. P less than 0.05 was considered significant. RESULTS. The mAPs in the CSA group generally remained lower than those of the CEA group. However, over the course of the operation as well as after repeated injections, the difference between the two groups decreased. Only at 5 min after administration of the initial dose was a statistically significant difference in blood pressures between the two groups observed. A clinically relevant, rapid decrease in blood pressure due to relatively high doses of LA was seen in 1 case in each group. The first reinjection of LA after the initial dose was after 1.9 h in the CSA group (bupivacaine HCl 0.5% 1 +/- 0.3 ml) and after 1.8 h in the CEA group (bupivacaine HCl 0.5% 4.5 +/- 1 ml). The total dose of bupivacaine in the CSA group was 0.18 ml/kg per hour versus 0.8 ml/kg in the CEA group. No post-dural puncture headache was observed in the CSA group. DISCUSSION. The catheter designed for CSA is easy to use, although because of its small diameter a certain manual dexterity is required. In addition, CSA resulted in a more rapid onset of action and more pronounced sensorimotor blockade than did CEA. Hemodynamic alterations and side effects were comparably low in both groups.

Aged↗