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K Ulrich

Publications and source records attributed to K Ulrich.

At least 19 recordsLinked to original sources
PubMed2005

Keratinocyte growth factor therapy in murine oleic acid-induced acute lung injury.

Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in PO2, PCO2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

Acute Disease↗
PubMed2003

Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo.

Repeat administration of gene therapy for cystic fibrosis is likely to be essential for long-term clinical efficacy. This may be minimized by the use of slow-release gene transfer preparations with more prolonged expression and longer dosing intervals for the patient. Poly(D-L-lactide-co-glycolide) (PLG) is a biodegradable and biocompatible polymer that has been used to encapsulate plasmid DNA. PLG-DNA microspheres were generated and characterized with respect to morphology, size (80% of particles <5.2 microm), and encapsulation efficiency (50.7+/-2.3%, n=6). Gel electrophoresis of DNA re-extracted from the microspheres confirmed that despite a decrease in the proportion of supercoiled conformation, it had not been degraded by the preparation process. Gene transfer efficiency was tested using microspheres encapsulating the reporter gene beta-galactosidase in vitro on Cos 7 cells and a CF airway epithelial line (CFTEo approximately ) and ex vivo in a sheep tracheal (s.t.) model. In both cases, transgene expression was significantly (P<0.01) lower at the first time point tested (24 h in vitro, 48 h ex vivo) compared to lipid-#67-mediated gene transfer. However, PLG-mediated expression in vitro was sustained at 48 h, while lipid #67-mediated expression levels had dropped significantly (P<0.05) to 50.3+/-13.7 and 38.2+/-2.7% (Cos 7 and CFTEo approximately cells, respectively) of the 24-h level. This pattern was also seen in the s.t. model where at 72 h, PLG-mediated expression was 125.4+/-7.2% of the 48-h level demonstrating significantly (P<0.05) better retention of transfection efficiency than lipid #67, where levels had fallen to approximately half the 48 h level. By 96 h, expression was still retained in the PLG-transfected group (87.3+/-12.5% of 48 h expression) but was undetectable in the lipid -#67-transfected s.t. Finally, PLG microspheres, encapsulating the reporter gene chloramphenicol transferase (CAT, 80 microg) were instilled intranasally into Balb/C mice. Compared to lipid-#67-mediated delivery, where whole lung CAT expression was highest at 48 h (13.7 x 10(3)+/-0.05 CAT U/microg protein, n=6) and then not detectable at further time points, CAT expression was not detectable in PLG-transfected mice at 48 h, but was detectable at 7, 14 and 21 days after transfection. These data demonstrate that PLG-mediated gene transfer can produce prolonged gene expression in airway epithelia. However, gene transfer efficiency still requires significant improvement.

Animals↗
PubMed2000

Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors.

BACKGROUND: Among patients with heart failure, there is controversy about whether there are clinical features and laboratory tests that can differentiate patients who have low ejection fractions from those with normal ejection fractions. The usefulness of angiotensin-converting enzyme (ACE) inhibitors among heart failure patients who have normal left ventricular ejection fractions is also not known. METHODS: From a registry of 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute-care community hospitals during 1995 and 1997, we identified 1291 who had a quantitative measurement of their left ventricular ejection fraction. Patients were separated into three groups based on ejection fraction: < or =0.39 (n = 741, 57%), 0.40 to 0.49 (n = 238, 18%), and > or =0.50 (n = 312, 24%). In-hospital mortality, prescription of ACE inhibitors at discharge, subsequent rehospitalization, quality of life, and survival were measured; survivors were observed for at least 6 months after hospitalization. RESULTS: The mean (+/- SD) age of the sample was 75+/-11 years; the majority (55%) of patients were women. In multivariate models, age >75 years, female sex, weight >72.7 kg, and a valvular etiology for heart failure were associated with an increased probability of having an ejection fraction > or =0.50; a prior history of heart failure, an ischemic or idiopathic cause of heart failure, and radiographic cardiomegaly were associated with a lower probability of having an ejection fraction > or =0.50. Total mortality was lower in patients with an ejection fraction > or =0.50 than in those with an ejection fraction < or =0.39 (odds ratio [OR] = 0.69, 95% confidence interval [CI 0.49 to 0.98, P = 0.04). Among hospital survivors with an ejection fraction of 0.40 to 0.49, the 65% who were prescribed ACE inhibitors at discharge had better mean adjusted quality-of-life scores (7.0 versus 6.2, P = 0.02), and lower adjusted mortality (OR = 0.34, 95% CI: 0.17 to 0.70, P = 0.01) during follow-up than those who were not prescribed ACE inhibitors. Among hospital survivors with an ejection fraction > or =0.50, the 45% who were prescribed ACE inhibitors at discharge had better (lower) adjusted New York Heart Association (NYHA) functional class (2.1 versus 2.4, P = 0.04) although there was no significant improvement in survival. CONCLUSIONS: Among patients treated for heart failure in community hospitals, 42% of those whose ejection fraction was measured had a relatively normal systolic function (ejection fraction > or 0.40). The clinical characteristics and mortality of these patients differed from those in patients with low ejection fractions. Among the patients with ejection fractions > or =0.40, the prescription of ACE inhibitors at discharge was associated favorable effects.

Aged↗
PubMed2000

The results of a randomized trial of a quality improvement intervention in the care of patients with heart failure. The MISCHF Study Investigators.

PURPOSE: Quality improvement and disease management programs for heart failure have improved quality of care and patient outcomes at large tertiary care hospitals. The purpose of this study was to measure the effects of a regional, multihospital, collaborative quality improvement intervention on care and outcomes in heart failure in community hospitals. PATIENTS AND METHODS: This randomized controlled study included 10 acute care community hospitals in upstate New York. After a baseline period, 5 hospitals were randomly assigned to receive a multifaceted quality improvement intervention (n = 762 patients during the baseline period; n = 840 patients postintervention), while 5 were assigned to a "usual care" control (n = 640 patients during the baseline period; n = 664 patients postintervention). Quality of care was determined using explicit criteria by reviewing the charts of consecutive patients hospitalized with the primary diagnosis of heart failure during the baseline period and again in the postintervention period. Clinical outcomes included hospital length of stay and charges, in-hospital and 6-month mortality, hospital readmission, and quality of life measured after discharge. RESULTS: Patients had similar characteristics in the baseline and postintervention phases in the intervention and control groups. Using hospital-level analyses, the intervention had mixed effects on 5 quality-of-care markers that were not statistically significant. The mean of the average length of stay among hospitals decreased from 8.0 to 6.2 days in the intervention group, with a smaller decline in mean length of stay in the control group (7.7 to 7.0 days). The net effects of the intervention were nonsignificant changes in length of stay of -1.1 days (95% confidence interval [CI]: -2.9 to 0.7 days, P = 0.18) and in hospital charges of -$817 (95% CI: -$2560 to $926, P = 0.31). There were small and nonsignificant effects on mortality, hospital readmission, and quality of life. CONCLUSIONS: The incremental effect of regional collaboration among peer community hospitals toward the goal of quality improvement was small and limited to a slightly, but not significantly, shorter length of stay.

Aged↗
PubMed2000

Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary oedema.

Resolution of pulmonary oedema is mediated by active absorption of liquid across the alveolar epithelium. A key component of this process is the sodium-potassium ATPase (Na+K+-ATPase) enzyme located on the basolateral surface of epithelial cells and up-regulated during oedema resolution. We hypothesised that lung liquid clearance could be further up-regulated by lipid-mediated transfer and expression of exogenous Na+K+-ATPase cDNA. We demonstrate proof of this principle in a model of high permeability pulmonary oedema induced by intraperitoneal injection of thiourea (2.5 mg/kg) in C57/BL6 mice. Pretreatment of mice (24 h before thiourea) by nasal sniffing of cationic liposome (lipid #67)-DNA complexes encoding the alpha and beta subunits of Na+K+-ATPase (160 microg per mouse), significantly (P<0.01) decreased the wet:dry weight ratios measured 2 h after thiourea injection compared with control animals, pretreated with an equivalent dose of an irrelevant gene. Whole lung Na+K+-ATPase activity was significantly (P<0.05) increased in mice pretreated with Na+K+-ATPase cDNA compared both with untreated control animals as well as animals pretreated with the irrelevant gene. Nested RT-PCR on whole lung homogenates confirmed gene transfer by detection of vector-specific mRNA in three of four mice studied 24 h after gene transfer. This demonstration of a significant reduction in pulmonary oedema following in vivo gene transfer raises the possibility of gene therapy as a novel, localised approach for pulmonary oedema in clinical settings such as ARDS and lung transplantation.

Animals↗
PubMed1999

Clinical outcomes in heart failure: report from a community hospital-based registry.

PURPOSE: Most of the recent information on the prognosis of patients with heart failure has come from large clinical trials or tertiary care centers. This study reports current information from a community hospital-based heart failure registry. SUBJECTS AND METHODS: We compiled data from 2,906 unselected consecutive patients with heart failure who were admitted to 10 acute care community hospitals in New York State between 1995 and 1997. Patients were followed prospectively for 6 months after hospital discharge or until their death. RESULTS: The mean (+/- SI)) age of the sample was 76 +/- 11 years. The majority of the patients were women (56%) and most were white (95%). Hospital length of stay averaged 7.4 +/- 7.6 days; hospital charges averaged $7,460 +/- $6,114. Mortality during the index admission was 5%. Among the 2,508 patients for whom mortality or follow-up data were available, an additional 411 died during follow-up, for a cumulative 6-month mortality of 23%. Progressive pump failure was the predominant cause of death in the hospital and after discharge. Although mean functional class (on a 1 to 4 scale) improved from 3.4 +/- 0.7 at hospital admission to 2.3 +/- 0.9 at 1 month after discharge, 43% of patients had at least one hospital readmission during follow-up and 25% had at least one recurrent admission for heart failure. The mean time from index discharge to first rehospitalization was 60 +/- 56 days. In all, 55% of patients (1,370 of 2,508) were rehospitalized or died during the study period. CONCLUSIONS: Despite advances in the management of heart failure, patients recently hospitalized for this disorder remain at high risk of death, hospital readmission, and poor clinical outcome. Discovery or implementation of new or existing methods of prevention and treatment remain a high priority.

Aged↗
PubMed1999

[Norms of arterial blood pressure for 24 hours based on biological activity].

So far there is no unambiguous universally accepted standards for 24 ABPM. Aim of this study was to establish standard values of systolic and diastolic blood pressures, taking into account minimal night values, corresponding with basic biological activity. 1204 patients were tested. In 707 of them, (mean age 42.5 +/- 14.7 years), arterial hypertension was recognized. Basic on our results we determined borderline values (112/69 mmHg) which are diagnostic for arterial hypertension. Those norms eliminate influence of environmental factors on values of blood pressure. They correspond with homeostasis in hypertensive patients.

Adult↗
PubMed1996

Does QI work? The Management to Improve Survival in Congestive Heart Failure (MISCHF) study.

BACKGROUND: In an ongoing study, a randomized, controlled trial is being conducted on the effects of a collaborative quality improvement program on practice patterns and patient outcomes regarding congestive heart failure (CHF) in community hospitals in upstate New York. CHF is associated with severe morbidity and mortality, with annual rates of death exceeding 50% among patients with the most severe disease. PHASE I: Phase I of the study was designed to model the processes of care and outcomes, develop valid disease-specific risk adjustment techniques, and target areas for quality improvement (QI) intervention. Beginning April 1, 1995, and ending December 31, 1995, baseline data were collected during hospitalization and for six months postdischarge for all 1,402 consecutive patients assigned diagnosis-related groups (DRGs) 127 and 124. Preliminary analyses revealed high rates of hospital readmission (46%) and postdischarge death (18%), with significant interhospital variation. QI INITIATIVES: Initiatives include educational programs on CHF, feedback of Phase I data to clinicians and administrators, design and implementation of a clinical care pathway, improvement of the emergency department (prehospital) phase of CHF management, and improvement in patient education and discharge planning. SUMMARY AND CONCLUSIONS: The study suggests that community hospitals, many without extensive experience in clinical investigation, can voluntarily collaborate to design and implement a timely QI initiative that is evidence based, clinically relevant, and scientifically sound. Preliminary results have led to better understanding of the processes of care and determinants of outcome for patients with heart failure. Phase II of the study should yield insights into the providers' response to a locally derived intervention and the effects of such a program on patient outcomes.

Cardiology Service, Hospital↗
PubMed1991

Competition ELISA using a human monoclonal antibody for detection of antibodies against human immunodeficiency virus type 1.

A novel competition ELISA for detection of antibodies against HIV-1 was developed. The assay is based on competition at the single epitope level and utilises a human monoclonal antibody and an E. coli-produced fragment of the transmembrane glycoprotein gp41. The sensitivity of the assay was 100% in tests on 247 serum samples obtained from 219 individuals previously shown to be HIV-1 antibody positive by both conventional indirect ELISA and the immunoblotting test. The patients represented various clinical and immunological stages of HIV-1 infection. Likewise, the specificity of the assay was 100% in tests on 105 serum samples from normal individuals previously tested negative by indirect ELISA. Further, among 105 serum samples selected due to consistent false positive reactions in the indirect ELISA only 2 samples (1.9%) demonstrated false positive reactions in the competition ELISA, i.e. 98.1% specificity. Finally, only 2 of 57 (3.5%) serum samples from HIV-2 infected individuals showed positive reactions in the assay, while 54 (94.7%) had absorbance values similar to the negative controls. These results demonstrate that human monoclonal antibodies may form the basis for highly sensitive and specific assays for detection of antibodies to HIV-1.

AIDS Serodiagnosis↗
PubMed1990

Characterization of a new malignant human T-cell line (PFI-285) sensitive to ascorbic acid.

A new malignant human T-cell line-labelled PFI-285-has been isolated from a boy with malignant lymphoma. Morphologically, the cells had characteristics of malignant lymphoid cells. The cells presented surface antigens as early cortical lymphocytes and proliferated non-adherently as single cells, independent of T-cell growth factor (IL-2), in liquid culture. The cells had undetectable levels of receptors for IL-2, were not clonogenic in soft agar, but did form tumors in nude mice. Their establishment and continuous growth in vitro was dependent on the number of cells inoculated and on the growth medium used. Cytogenetic alteration, HTLV-1 or reverse transcriptase activity were not detected. The production of known T-cell derived lymphokines such as IL-2, B-cell growth factor(s), alpha-interferon or granulocyte/macrophage colony stimulating or inhibiting factor(s) was not detected. The cells had 5-8% natural killer (NK)-cell activity against NK-cell sensitive target cells (K562) and were not sensitive for NK cells. A most unusual characteristic was the pronounced sensitivity of the cells to ascorbic acid. Concentrations down to 50 mumol/l killed the cells within hours.

Adolescent↗
PubMed1990

Analysis of a highly immunodominant epitope in the human immunodeficiency virus type 1 transmembrane glycoprotein, gp41, defined by a human monoclonal antibody.

A human monoclonal antibody, 41-7 [immunoglobulin G1(kappa)], directed against the transmembrane glycoprotein gp41 of the human immunodeficiency virus type 1 (HIV-1) has been produced by direct fusion of lymph node cells from an HIV-1-infected individual with a human B-lymphoblastoid cell line. The minimal essential epitope for 41-7 was mapped to a conserved seven-amino acid sequence, N-CSGKLIC-C, located within the N-terminal part of gp41. Antibodies blocking the binding of 41-7 could be detected in the serum of all HIV-1-infected individuals tested, irrespective of the stage of the infection. The epitope is located externally to the plasma membrane, and it is accessible to antibody in the native conformation of the glycoprotein. Despite this, no neutralizing activity of 41-7 could be demonstrated in vitro. These data indicate, directly and indirectly, that this immunodominant epitope on gp41, although exposed on the viral surface, elicits antibodies lacking antiviral activity and, hence, should be avoided in future vaccine candidates.

Amino Acid Sequence↗
PubMed1990

[Freckles and dysplasias of the eyebrows as indicators for genetic abnormalities of the development of the teeth and the jaws].

For the first time the frequency of freckles and of dysplasias of the eyebrows was examinated in 756 pupils. The percentage of the freckles was 21, and of the dysplasias of the eyebrows 28.5 in both sexes. The following examination of 287 orthodontic patients (66 males with hypodontia, 60 males with normal number of the teeth; 92 females with hypodontia, 69 females with normal number of the teeth) has demonstrated the high significance of incidence of freckles and of dysplasias of the eyebrows in patient with hypodontia. This phenomenon is important, because extraoral stigmatas can indicate to disturbances of the development of teeth and also to anomalies of the number of the teeth.

Anodontia↗
PubMed1989

Antibodies against the major core protein p24 of human immunodeficiency virus: relation to immunological, clinical and prognostic findings.

In 79 homosexual men positive for antibody to human immunodeficiency virus (HIV), the titer and avidity of p24 antibody was determined by an indirect ELISA and the serum tested for the presence of HIV antigen. Results were examined for a possible correlation with clinical, immunological and prognostic findings. High titers and low avidity of p24 antibodies correlated significantly with a normal pokeweed mitogen response, early lymph node changes, and an asymptomatic and stable clinical condition. In HIV antigen negative patients, low titers and high avidity of p24 antibodies correlated significantly with a progressive clinical condition. The finding of primarily high avidity antibodies against p24 antigen in patients with more advanced immunodeficiency indicates that a decline of p24 antibodies during the clinical course of HIV infection may not be explained exclusively by an increased production of viral proteins.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Isolated canine aplasia in monozygotic twins].

This article describes isolated aplasia of the upper canines with retained deciduous canines in identical female twins. The twins are also concordant in some ectodermal stigmata. As a result of investigating other members of the family it appears that aplasia of the canines is due to a specific autosomal dominant gene.

Adolescent↗
PubMed1989

HIV neutralizing antibodies: development and association with HIV related disease.

Serum neutralization was measured in 72 sera collected during a 5.5-year period from 10 HIV infected individuals. Neutralizing antibodies (NA) were present in all sera. NA titers ranging from greater than 40 to greater than 640 were detected in sera from 4 patients, who all remained healthy and further an increase with time of NA was observed in these 4 patients. Progression to disease was observed in 3 persons with NA titers less than or equal to 40 who also lacked or lost anti-gag antibodies. Two of these patients were HIV antigenaemic prior to development of disease, whereas antigen was not detected in the remaining 7 healthy persons. A weak positive correlation (R(S) = +0.643, p less than 0.001) was found between titers of NA and whole virus antibody (WVA), with the ratios between titers (NA titer/WVA titer) varying a 100-fold. The results suggest that the presence of NA in some cases might be related to a healthy carrier state and that a combination of low titer NA with decline of anti-gag antibodies and/or HIV antigenaemia is associated with progression to clinical disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Serological markers of primary HIV infection.

39 persons with an incidentally discovered seroconversion from HIV antibody negative (Ab-) to antibody positive (Ab+) state as measured by an enzyme-linked immunosorbent assay (ELISA) were investigated for the presence of (1) HIV antigen (Ag) and (2) immunoblotting test (IBT) Ab in serum samples collected within the year before seroconversion. 13 (33%) of the patients were HIV Ag+ at some time before seroconversion. However, the collection of samples was not done systematically and the samples from patients who had at least 1 sample collected within 3 months before seroconversion were thus compiled separately. This group consisted of 58 samples from 19 patients and among these none were HIV Ag+ earlier than 11 weeks before seroconversion, but the prevalence of HIV Ag+ samples was rising towards seroconversion and 10 patients (53%, 95% confidence limits: 29-76%) became HIV Ag+ in this 11-week period. Further, among all patients 13 (33%) were IBT Ab+ 4-50 days (median: 14 days) before seroconversion. Finally, among 18 patients with signs and symptoms consistent with an acute HIV infection 10 were HIV Ag+, as opposed to 4 HIV Ag+ patients among 21 without symptoms (p = 0.041).

Adolescent↗