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Biomedical subjects

L Ludwig

Publications and source records attributed to L Ludwig.

At least 19 recordsLinked to original sources
PubMed2006

Laparoscopic partial splenectomy.

BACKGROUND: The immunologic function of the spleen and its important role in immune defense has led to splenic-preserving surgery. This study aimed to evaluate whether laparoscopic partial splenectomy is safe. METHODS: Data on consecutive patients presenting with localized benign or malignant disease of the spleen were included in a prospective database. The surgical technique consisted of six steps: patient positioning and trocar placement, mobilization of the spleen, vascular dissection, parenchymal resection, sealing/tamponading of the transected edge, and removal of the specimen. RESULTS: From 1994 to 2005, 38 patients underwent laparoscopic partial splenectomy. The indications included splenomegaly of unknown origin, splenic cysts, benign tumors (hamartoma), and metastasis from ovarian carcinoma and schwannoma. The median operating time was 110 min (range, 65-148 min). The median length of hospital stay was 5 days (range, 4-7 days). There was no postoperative mortality. Postoperative pleural effusion occurred in two patients. There were no reoperations. Three patients required blood transfusions. CONCLUSION: Laparoscopic partial splenectomy is safe for patients with localized benign or malignant disease of the spleen.

Adolescent↗
PubMed2001

Nuclear factor-kappaB is constitutively active in C-cell carcinoma and required for RET-induced transformation.

Specific point mutations of the RET proto-oncogene have been demonstrated to be responsible for multiple endocrine neoplasia (MEN) types 2A and 2B, for familial medullary thyroid carcinoma (MTC) syndromes, as well as for sporadic MTC. Here we show that nuclear factor (NF)-kappaB is activated in RET-associated C-cell carcinoma specimens. TT cells, a human MTC cell line expressing MEN 2A type RET, display transcriptionally active RelA(p65) in the nucleus. NF-kappaB activity in these cells is attributable to constitutive IkappaB kinase (IKK) activity and high turn over of IkappaBalpha. RET harboring the mutations C634R (MEN 2A) or M918T (MEN 2B), in contrast to wild-type RET, activates a NF-kappaB-dependent reporter construct upon transient transfection in HeLa cells. We show that the prototype RET mutation C634R enhances phosphorylation of IkappaBalpha by IKKbeta but not by IKKalpha. RET-induced NF-kappaB and IKKbeta activity requires Ras function but does neither involve the classical mitogen-activated protein kinase kinase/extracellular signal-regulated kinase nor the phosphoinositide 3-kinase/Akt pathways. In contrast, RET-induced NF-kappaB activity is dependent on Raf and MEKK1. Inhibition of constitutive NF-kappaB activity results in cell death of TT cells and blocks focus formation induced by oncogenic forms of RET in NIH 3T3 cells. These results suggest that RET-mediated carcinogenesis critically depends on IKK activity and subsequent NF-kappaB activation.

3T3 Cells↗
PubMed2001

Designing a library: everyone on the same page?

Excerpts are presented from an interview by the Bulletin of the Medical Library Association buildings projects editor with four academic health sciences library directors: one who had recently completed a major library building project and three who were involved in various stages of new building projects. They share their experiences planning for and implementing library-building programs. The interview explores driving forces leading to new library buildings, identifies who should be involved, recalls the most difficult and exciting moments of the building projects, relates what they wished they had known before starting the project, assesses the impact of new library facilities on clients and services, reviews what they would change, and describes forces impacting libraries today and attributes of the twenty-first century library.

Architecture↗
PubMed1999

Loss of wild-type MEN1 gene expression in multiple endocrine neoplasia type 1-associated parathyroid adenoma.

Multiple endocrine neoplasia type 1 (MEN1) is a human hereditary tumor syndrome characterized by the development of endocrine adenomas of the parathyroid, anterior pituitary, and enteropancreatic tissue. Several lines of evidence have implicated the recently identified MEN1 gene located on chromosome 11q13 as a recessive tumor suppressor gene. Here, we analyzed MEN1 wild-type gene expression in tumors from a large MEN1 kindred. A deletion of codons 227-228 (678del6) located in exon 4 was found in tumor and peripheral blood complementary DNA using a simplified single-strand conformational polymorphism (SSCP) approach well suited for clinical MEN1 mutation screening. The identified 678del6 cDNA mutation deletes a potential phosphorylation site (Tyr227) and corresponds to a germ line mutation co-segregating with disease phenotype in this MEN1 family. Loss of heterozygosity analysis by fluorescent microsatellite PCR showed an exclusive loss of the MEN1 wild-type (and retention of the mutated) allele detectable in DNA from microdissected parathyroid and pancreatic, but not in adrenal, adenomas. Our findings confirm the synergism between MEN1 gene mutations and subsequent MEN1 allelic losses in the tumorigenesis of MEN1-associated adenomas.

Adenoma↗
PubMed1999

[Obstructive malformation of the verumontanum].

The authors report the case of a 23-year-old man presenting with obstructive polypoid hyperplasia of the verumontanum, 4 cm long, inducing dysuria with residual urine, demonstrated on urethroscopy and requiring endoscopic resection. The symptoms resolved completely after treatment.

Adult↗
PubMed1998

Menin mutations in the diagnosis and prediction of multiple endocrine neoplasia type 1.

INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the development of multiple endocrine adenomas, typically in the pancreas, anterior pituitary, and parathyroid glands. The disease is associated with germ-line mutations of the menin gene, a putative tumor-suppressor gene located on human chromosome 11q13. METHODS: To facilitate the diagnosis and prediction of MEN1 in patients and their relatives, we developed a molecular two-step strategy to screen for menin gene mutations. DNA fragments covering the entire menin coding sequence are generated from patient cDNA by polymerase reaction (PCR) and subsequently analyzed by single-strand conformational polymorphism electrophoresis (SSCP). Fragments with aberrant SSCP migration are DNA-sequenced to directly characterize menin mutations. In a second diagnostic step, genomic DNA of healthy relatives of the corresponding MEN1 index patient is analyzed by PCR, with only the specific exon amplified harboring the family-specific mutation. Mutation-specific restriction enzyme digestion of this PCR product finally allows the identification of mutation carriers through pathological restriction fragment patterns. RESULTS: Using this approach, we identified an in-frame deletion mutation (delta Tyr Met) located in menin exon 4 (codon 227-228) that co-segregates with the disease phenotype in a large MEN1 family from Southern Germany. CONCLUSION: It is likely that the direct molecular analysis of menin gene mutations will replace the genetic and biochemical screening tests currently used in the clinical management of MEN1 families. In addition, these studies may provide clues to the tumor biology of both sporadic and MEN1-associated endocrine adenomas.

Adult↗
PubMed1998

Cardiac troponin I as a predictor of major cardiac events in emergency department patients with acute chest pain.

OBJECTIVES: We sought to evaluate the diagnostic and prognostic value of cardiac troponin I (cTnI) in emergency department (ED) patients with chest pain. BACKGROUND: Although cTnI has been shown to correlate with an increased risk for complications in patients with unstable angina, the prognostic significance of this assay in the heterogeneous population of patients who present to the ED with chest pain is unclear. METHODS: cTnI and creatine kinase-MB fraction (CK-MB) mass concentration were collected serially during the first 48 h from onset of symptoms in 1,047 patients > or =30 years old admitted for acute chest pain. Sensitivity, specificity and receiver operating characteristic curves were calculated for cTnI and CK-MB collected in the first 24 h. RESULTS: The sensitivity, specificity and positive predictive value of cTnI for major cardiac events were 47%, 80% and 19%, respectively. Among patients were who ruled out for myocardial infarction, cTnI was elevated in 26% who had major cardiac complications compared with 5% for CK-MB; the positive predictive value for an abnormal cTnI result was 8%. Elevated cTnI in the presence of ischemia on the electrocardiogram was associated with an adjusted odds ratio of 1.8 (95% confidence interval 1.1 to 2.9) for major cardiac events within 72 h. Among patients without a myocardial infarction or unstable angina, cTnI was not an independent correlate of complications. CONCLUSIONS: In patients presenting to the ED with acute chest pain, cTnI was an independent predictor of major cardiac events, However, the positive predictive value of an abnormal assay result was not high in this heterogeneous cohort.

Adult↗
PubMed1997

Body mass index as a correlate of postoperative complications and resource utilization.

PURPOSE: To describe the relationship of body mass index (BMI) with postoperative complications and resource utilization. PATIENTS AND METHODS: Two thousand nine hundred and sixty-four patients 50 years or older undergoing elective noncardiac surgery with an expected length of stay > or = 2 days were enrolled in a prospective cohort study to measure major cardiac complications, noncardiac complications, length of stay, and costs. The setting was an urban teaching hospital. A preoperative history, physical, electrocardiogram (ECG), and chart review were performed by study personnel. Postoperative complications were detected by ECGs, creatine kinase and creatine kinase MB levels, and daily chart review. Total costs were obtained from the hospital's computerized database. RESULTS: Complication rates were not different among BMI groups (underweight < 20, normal 20 to 29, overweight 30 to 34, most overweight > 34), but patients with BMI 30 to 34 and > 34 who underwent abdominal or gynecologic procedures had significantly higher wound infection rates (11% each) than normal weight patients (4.7%) or the underweight (0%). After adjusting for age, race, gender, smoking history, comorbid diseases, procedure type, and insurance status, there were nonsignificant trends toward increased resource utilization by the most overweight patients (BMI > 34). These patients stayed 0.8 days longer (P = 0.13) and had total costs that were $843 higher (P = 0.17) than patients of normal weight (BMI 20 to 29). The underweight patients stayed 0.9 days longer (P = 0.23) and had total costs that were $3,150 higher (P = 0.04) than patients of normal weight. Quadratic models to test for a U-shaped relationship found no correlation between BMI and length of stay, but did find that BMI was significantly correlated with total costs (P = 0.04). This relationship persisted when patients who had complications were excluded from the analysis. CONCLUSIONS: Overall, BMI was not significantly correlated with postoperative complications or length of stay. However, overweight patients who underwent abdominal or gynecologic procedures had higher wound infection rates, and patients with the highest and lowest BMIs had significantly higher adjusted total costs.

Age Distribution↗
PubMed1996

RAG mutations in human B cell-negative SCID.

Patients with human severe combined immunodeficiency (SCID) can be divided into those with B lymphocytes (B+ SCID) and those without (B- SCID). Although several genetic causes are known for B+ SCID, the etiology of B- SCID has not been defined. Six of 14 B- SCID patients tested were found to carry a mutation of the recombinase activating gene 1 (RAG-1), RAG-2, or both. This mutation resulted in a functional inability to form antigen receptors through genetic recombination and links a defect in one of the site-specific recombination systems to a human disease.

B-Lymphocytes↗
PubMed1996

Noninvasive positive-pressure ventilation in acute respiratory distress without prior chronic respiratory failure.

We evaluated the efficacy of noninvasive mechanical ventilation (NIMV) in alleviating distress and avoiding intubation in patients with de novo acute respiratory failure complicating primary medical disorders. Eleven consecutive patients with severe respiratory distress were entered. In all patients a decision to intubate on an urgent basis had been made, but NIMV could be initiated within minutes. The patients suffered from acute pulmonary edema (five), sepsis/ARDS (two), status asthmaticus (two), and severe pneumonia (two). Dyspnea score (max=10) was (+/- SD) 8.4 +.- 1.6, scale for accessory muscle use (max=5) was 4.2 +/- 0.7, and respiratory rate was 37.6 +/- 3.8 min -1. Pa CO2, pH, and base excess (BE) were 48 +/- 18 mm Hg, 7.27 +/- 0.13, and -5.5 +/- 7.4, respectively, with five patients showing severe metabolic acidosis (BE < - 10). NIMV was applied using proportional assist ventilation. There were three early failures. These included the two patients with sepsis/ARDS who did not tolerate the mask. One patient failed because Pa CO2 and pH deteriorated despite subjective improvement. The remaining eight patients demonstrated progressive improvement, and none required intubation. The duration of NIMV was 3 h to 2 d. We conclude that when NIMV is made available on a "few minutes" basis, selected patients with severe de novo respiratory distress/failure caused by reversible medical disorders, who would otherwise have been intubated, can be given substantial relief and be spared intubation.

Acid-Base Imbalance↗
PubMed1996

Health sciences library building projects: 1995 survey.

The Medical Library Association's fifth annual survey of recent health sciences library building projects identified twenty-five libraries planning, expanding, or constructing new library facilities. None of the fifteen new library projects are free standing structures; however, several occupy a major portion of the project space. Ten projects involve renovation of or addition to existing space. Information regarding size, cost of project, type of construction, completion date, and other factual data was provided for twelve projects. The remaining identified projects are in pre-design or early-design stages, or are awaiting funding approval. Library building projects for three hospital libraries, three academic medical libraries, and an association library are described. Each illustrates how considerations of economics and technology are changing the traditional library model from a centrally stored information depository housing a wide range of information under one roof where users come to the information, into an electronic model gradually shifting from investment in the physical presence of resources to investment in creating work space for creditible information specialists who help in-house and distanced users to obtain information electronically from any place and at any time. This new model includes a highly skilled library team to manage, filter, and package the information to users trained by these resident experts.

Canada↗
PubMed1996

[Ovarian angioma. Report of 3 asymptomatic cases].

In 3 female patients, aged 46, 50 and 74 years respectively, ovarian angiomas measuring 3, 5 and 30 mm in diameter were discovered. All the angiomas were asymptomatic. They were either associated with endometrioid carcinoma or uterine leiomyomas, or detected casually by ultrasound scan in a patient with ascites, intrahepatic nodule and increased serologic CA 125. The immunohistochemical studies failed to reveal any affinity between the vascular endothelium of our ovarian angiomas and oestrogen and progesterone receptors.

Aged↗
PubMed1995

A randomized, double-blind comparison of methoxamine and epinephrine in human cardiopulmonary arrest.

The beneficial effect of epinephrine has been attributed to its alpha-adrenergic properties. The present study was designed to compare the effects of epinephrine and methoxamine in witnessed cardiac arrests. Consecutive, witnessed cardiac-arrest victims presenting to the emergency room or from the inpatient population of our institution were enrolled in this study. Patients were randomized to receive either epinephrine (2 mg bolus followed by 2 mg every 4 min) or methoxamine (40 mg bolus followed after 4 min by 40 mg) in a blind design. Patients were followed prospectively for survival and neurologic outcome. A total of 199 patients were randomized into the study, but 54 had to be retrospectively dropped from analysis for failure to comply with the study protocol. Of the 145 patients remaining, 77 received methoxamine (M) and 68 epinephrine (E). There was no difference in rate of successful resuscitation (42% versus 53%, M versus E, respectively), or in neurologic outcome as measured by the Glasgow-Pittsburgh Coma Score (GPCS). This study failed to demonstrate any difference in the rate of initial resuscitation, survival to discharge from the hospital, or neurologic status with methoxamine as opposed to epinephrine in the setting of cardiac arrest.

Adult↗
PubMed1995

Health sciences library building projects: 1994 survey.

Designing and building new or renovated space is time consuming and requires politically sensitive discussions concerning a number of both long-term and immediate planning issues. The Medical Library Association's fourth annual survey of library building projects identified ten health sciences libraries that are planning, expanding, or constructing new facilities. Two projects are in predesign stages, four represent new construction, and four involve renovations to existing libraries. The Texas Medical Association Library, the King Faisal Specialist Hospital and Research Centre Library, and the Northwestern University Galter Health Sciences Library illustrate how these libraries are being designed for the future and take into account areas of change produced by new information technologies, curricular trends, and new ways to deliver library services.

Chicago↗
PubMed1995

Exon trap analysis of a NF1 splice-site mutation in a chronic myelomonocytic leukemia patient.

We have previously described a patient with chronic myelomonocytic leukemia who exhibited a mutation (del-10:-8) in the splice-acceptor region in front of the FLR exon of the NF1 tumor suppressor gene. In order to evaluate whether this mutation indeed affects correct splicing of this exon we used an exon trap approach. Our data unequivocally prove the functional relevance of this NF1 mutation. Exon trapping thus represents an attractive strategy to study the consequences of putative splice-site mutations if RNA samples are not available.

Base Sequence↗