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Biomedical subjects

P Linden

Publications and source records attributed to P Linden.

At least 19 recordsLinked to original sources
PubMed2006

Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature.

Zygomycetes are ubiquitous fungi that can cause invasive disease associated with high mortality. We report 10 solid organ transplant recipients with zygomycosis (incidence 2 per 1000) and reviewed 106 cases in the English-language literature. These included renal (n = 73), heart (n = 16), lung (n = 4), heart/lung (n = 2), liver (n = 19) and kidney/pancreas (n = 2) transplant recipients. All patients were receiving immunosuppression and the vast majority steroids. The clinical presentation included rhino-sino-orbital (n = 20), rhinocerebral (n = 16), pulmonary (n = 28), gastrointestinal (n = 13), cutaneous (n = 18), renal (n = 6) and disseminated disease (n = 15). Most frequently isolated genera were Rhizopus (73%) followed by Mucor (13%). The overall mortality was 49%. While rhino-sino-orbital disease had the best prognosis, rhinocerebral disease had high mortality (93%) comparable to disseminated disease. A favorable outcome was associated with limited, surgically accessible disease and early surgical intervention along with amphotericin B administration.

Hospitals, University↗
PubMed2002

Esophagectomy for esophageal cancer.

This review considers the esophagectomy techniques in the treatment of esophageal cancer and provides the guidelines for optimizing the patients' chances at cure, minimizing the risk of mediastinal enteric leak (which carries a mortality rate as high as 50%) and minimizing associated pulmonary insufficiency and infection. The 4 most commonly used routes for resection and replacement include a transhiatal, transthoracic (Ivor-Lewis), tri-incisional (right chest then simultaneous abdominal and left neck), and left chest (distal tumors). Each of these techniques will be described as will the use of colon and jejunum for esophageal replacement. The healthy stomach is the preferred conduit for esophageal replacement. The stomach is well vascularized, easily reaches to the neck, and requires only a single anastomosis for re-establishing intestinal continuity. When the stomach is not available (usually because of prior surgery or disease) the choice of conduits include colon and jejunum. With respect to minimally invasive esophagectomy for esophageal cancer, several groups have significant experience with this and report excellent results. This is an evolving technique but holds much promise for improving the quality of life of patients with cancer without compromising their survival. In locally advanced middle third tumors, thoracotomy and dissection under direct vision's desirable and improves the safety of the operation. The same may apply to tumors receiving neoadjuvant therapy. For tumors of the distal esophagus, transhiatal, tri-incisional, and Ivor-Lewis resection are probably equally as safe, and appear to result in equivalent long-term survival. An intrathoracic anastomotic leak is disastrous, carrying a mortality rate of up to 50%. Any surgeon who performs esophagectomy with an intrathoracic anastomosis must do so with a low incidence of leakage, certainly under 5%. Consideration should be given to a cervical placement if there are factors increasing the risk such as the use of induction therapy.

Colon↗
PubMed2001

Effective suppression of vancomycin-resistant Enterococcus species in asymptomatic gastrointestinal carriers by a novel glycolipodepsipeptide, ramoplanin.

Nosocomial bloodstream infections due to vancomycin-resistant enterococci (VRE) are associated with increased morbidity rates, mortality rates, and hospitalization costs. Gastrointestinal carriage of VRE is an important risk factor for subsequent infections. This 3-arm, phase II, double-blinded, randomized, multicenter, placebo-controlled study evaluated the safety and efficacy of oral ramoplanin (a novel, nonabsorbed glycolipodepsipeptide) versus placebo for suppression of gastrointestinal VRE colonization. Sixty-eight patients who were colonized with VRE were enrolled and received 2 daily doses of ramoplanin (100 mg or 400 mg) or placebo orally for 7 days. The primary end point was the proportion of persons per group from whom VRE were not recovered (VRE-free) on days 7, 14, and 21 after screening. After treatment, VRE-free status was as follows: day 7, none of the 20 patients in the placebo group, and 17 of 21 (P<.001) and 18 of 20 (P<.001) in the 100-mg and 400-mg ramoplanin groups, respectively; on day 14, 2 of 20 patients in the placebo group, and 6 of 21 (P=.134) and 7 of 17 (P=.028), in the 100-mg and 400-mg ramoplanin groups, respectively. By day 21, there were no differences between treatment groups. Adverse events were similar for all treatment groups. Ramoplanin was safe and effective in temporarily suppressing gastrointestinal VRE carriage.

Adult↗
PubMed2001

Acute respiratory failure associated with pulmonary cryptococcosis in non-aids patients.

PURPOSE: To determine the incidence of acute respiratory failure (ARF) in non-AIDS patients with pulmonary cryptococcosis (PC). DESIGN: Retrospective cohort study. SETTING: University of Pittsburgh Medical Center, Pittsburgh, PA. SUBJECTS: All patients in whom PC without HIV infection was diagnosed between February 1989 and March 1999. RESULTS: Thirty-three patients with PC were identified, and 11 of those patients (33%) developed ARF and comprised the study group. Underlying diseases included solid-organ transplant recipients (seven patients; 64%) and other underlying medical conditions (four patients; 36%). The most common symptoms were cough, shortness of breath, and temperature elevation. Extrapulmonary involvement was seen in six patients (meningitis, four patients; peritonitis, one patient; laryngeal mass, one patient). Six of the 11 patients (55%) died. CONCLUSION: ARF may develop in one third of non-AIDS patients with PC. This clinical syndrome is associated with the dissemination to extrapulmonary sites and high mortality rates. PC should be recognized as a possible cause of respiratory failure in non-AIDS patients.

Acute Disease↗
PubMed2000

Efficacy and safety of amphotericin B lipid complex injection (ABLC) in solid-organ transplant recipients with invasive fungal infections.

BACKGROUND: Fungal infections following solid-organ transplantation are a major source of morbidity and mortality. This report describes the efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients. METHODS: Three open-label, second-line treatment studies evaluated ABLC as a treatment for severe, life-threatening mycoses in patients who were refractory to or intolerant to conventional antifungal (mostly amphotericin B [AmB]) therapy or had pre-existing renal disease. RESULTS: The 79 solid-organ transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1 pancreas) who received ABLC in these studies had the following fungal infections: aspergillosis (n = 39); candidiasis (n = 20); zygomycosis (n = 8); cryptococcosis and histoplasmosis (n = 3 each); and blastomycosis, cladosporiosis, fusariosis, Bipolaris hawaiiensis, Dactylaria gallopava, and an unspecified fungal infection (n = 1 each). The median duration of ABLC therapy was 28 d (1-178 d). The daily dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response rate for the patients who could be assessed was 58% (39/67). Clinical response rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%, respectively; response rates for aspergillosis and candidiasis were 47 and 71%, respectively. Forty-six of the 79 patients (58%) survived for more than 28 d after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64 patients (81%) had stable (n = 37) or improved (n = 27) serum creatinine at the end of treatment. CONCLUSIONS: ABLC is safe and effective treatment for fungal infections in solid-organ transplant recipients. Its renal-sparing properties are particularly suited for this high-risk population for renal failure.

Adolescent↗
PubMed1999

Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis.

Proteolytic enzymes are involved in generation of a number of endogenous angiogenesis inhibitors. Previously, we reported that angiostatin, a potent angiogenesis inhibitor, is a proteolytic fragment containing the first four kringle modules of plasminogen. In this report, we demonstrate that urokinase-activated plasmin can process plasminogen to release an angiogenesis inhibitor, K1-5 (protease-activated kringles 1-5). K1-5 inhibits endothelial-cell proliferation with a half-maximal concentration of approximately 50 pM. This inhibitory effect is endothelial-cell-specific and appears to be at least approximately 50-fold greater than that of angiostatin. A synergistic efficacy of endothelial inhibition was observed when angiostatin and kringle 5 (K5) were coincubated with capillary endothelial cells. The synergistic effect is comparable to that produced by K1-5 alone. Systemic treatment of mice with K1-5 at a low dose significantly blocked the fibroblast growth factor-induced corneal neovascularization, whereas angiostatin had no effect at the same dose. K1-5 also suppressed angiogenesis in chicken embryos. Systemic administration of K1-5 at a low dose at which angiostatin was ineffective significantly suppressed the growth of a murine T241 fibrosarcoma in mice. The antitumor effect correlates with the reduced neovascularization. These findings suggest that the plasmin-mediated proteolysis may be involved in the negative switch of angiogenesis.

Angiostatins↗
PubMed1999

Quinupristin-Dalfopristin.

The incidence of infection with multidrug-resistant or pan-resistant gram-positive bacteria has drastically limited or eliminated the conventional antimicrobial options available to clinicians. Quinupristin-dalfopristin, a unique parenteral streptogramin that lacks cross-resistance with other antimicrobials, has shown clinical efficacy against many of these important bacteria. This review focuses on quinupristin-dalfopristin"s mechanism of action, in vitro spectrum of activity, clinical efficacy and toxicity, and likely future role in the management of serious gram-positive infections.

Journal Article↗
PubMed1999

Retrospective analysis of the dosage of amphotericin B lipid complex for the treatment of invasive fungal infections.

STUDY OBJECTIVE: To understand the relationship between dosage and therapeutic response of amphotericin B lipid complex (ABLC) by analyzing underlying diseases, types of infections, and therapeutic outcomes with different dosages as second-line antifungal therapy. DESIGN: Retrospective analysis of low-dose (initial dose < or = 3 mg/kg) ABLC from three open-label, clinical, second-line treatment studies. SETTING: Centers in the United States (204), Canada (3), Australia (1), Mexico (1), and The Netherlands (1). PATIENTS: Five hundred fifty-one patients (5 enrolled twice) with invasive fungal infections, of whom 289 failed and 267 were intolerant to conventional antifungal therapy. INTERVENTIONS: Patients were to receive the recommended dosage of ABLC 5 mg/kg/day, with dosage reduction for markedly increased serum creatinine. The duration of treatment was 4 weeks; therapy could be extended if the investigator considered additional treatment necessary. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients (13%) received ABLC 3 mg/kg/day (low dosage) instead of the protocol-recommended 5 mg/kg/day Response was 65% and 56%, respectively. Logistic regression analysis revealed that the following patients are most likely to start therapy at the lower dosage: those with candidiasis and other yeast infections, patients with nephrotoxicity due to prior amphotericin B, and those with underlying conditions other than hematologic malignancy. CONCLUSION: These results suggest that ABLC 3 mg/kg/day may be effective in treating patients with candidiasis who do not have hematologic malignancy.

Adolescent↗
PubMed1998

Vascular endothelial growth factor C induces angiogenesis in vivo.

Vascular endothelial growth factor C (VEGF-C) recently has been described to be a relatively specific growth factor for the lymphatic vascular system. Here we report that ectopic application of recombinant VEGF-C also has potent angiogenic effects in vivo. VEGF-C is sufficiently potent to stimulate neovascularization from limbal vessels in the mouse cornea. Similar to VEGF, the angiogenic response of corneas induced by VEGF-C is intensive, with a high density of new capillaries. However, the outgrowth of microvessels stimulated by VEGF-C was significantly longer than that induced by VEGF. In the developing embryo, VEGF-C was able to induce branch sprouts from the established blood vessels. VEGF-C also induced an elongated, spindle-like cell shape change and actin reorganization in both VEGF receptor (VEGFR)-2 and VEGFR-3-overexpressing endothelial cells, but not in VEGFR-1-expressing cells. Further, both VEGFR-2 and VEGFR-3 could mediate proliferative and chemotactic responses in endothelial cells on VEGF-C stimulation. Thus, VEGF-C may regulate physiological angiogenesis and participate in the development and progression of angiogenic diseases in addition to lymphangiogenesis.

Allantois↗
PubMed1998

Practice guidelines for evaluating new fever in critically ill adult patients. Task Force of the Society of Critical Care Medicine and the Infectious Diseases Society of America.

OBJECTIVE: The development of practice guidelines for evaluating adult patients who develop new fever in the intensive care unit (ICU) for the purpose of guiding clinical practice. PARTICIPANTS: A task force of 13 experts in disciplines related to critical care medicine, infectious diseases, and surgery was convened from the membership of the Society of Critical Care Medicine and the Infectious Disease Society of America. EVIDENCE: The task force members provided personal experience and determined the published literature (articles retrieved with use of MEDLINE or textbooks) from which consensus would be sought. The published literature was reviewed and classified into one of four categories, according to study design and scientific value. CONSENSUS PROCESS: The task force met several times in person and twice monthly by teleconference over a 1-year period to identify the pertinent literature and arrive at consensus recommendations. Consideration was given to the relationship between the weight of scientific evidence and the experts' opinions. Draft documents were composed and debated by the task force until consensus was reached by nominal group process. CONCLUSIONS: The panel concluded that because fever can have many infectious and noninfectious etiologies, a new fever in an adult patient in the ICU should trigger a careful clinical assessment rather than automatic orders for laboratory and radiological tests. A cost-conscious approach to obtaining diagnostic studies should be undertaken if they are indicated after a clinical evaluation. The goal of such an approach is to determine, in a directed manner, whether infection is present so that additional testing can be avoided and therapeutic options can be identified.

Adult↗
PubMed1998

Practice parameters for evaluating new fever in critically ill adult patients. Task Force of the American College of Critical Care Medicine of the Society of Critical Care Medicine in collaboration with the Infectious Disease Society of America.

OBJECTIVE: To develop practice parameters for the evaluation of adult patients who develop a new fever in the intensive care unit (ICU) for the purpose of guiding clinical practice. PARTICIPANTS: A task force of 13 experts in disciplines related to critical care medicine, infectious diseases, and surgery was convened from the membership of the Society of Critical Care Medicine, and the Infectious Disease Society of America. EVIDENCE: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four categories, according to study design and scientific value. CONSENSUS PROCESS: The task force met several times in person and twice monthly by teleconference over a 1-yr period of time to identify the pertinent literature and arrive at consensus recommendations. Consideration was given to the relationship between the weight of scientific evidence and the experts' opinions. Draft documents were composed and debated by the task force until consensus was reached by nominal group process. CONCLUSIONS: The panel concluded that, because fever can have many infectious and noninfectious etiologies, a new fever in a patient in the ICU should trigger a careful clinical assessment rather than automatic orders for laboratory and radiologic tests. A cost-conscious approach to obtaining cultures and imaging studies should be undertaken if it is indicated after a clinical evaluation. The goal of such an approach is to determine, in a directed manner, whether or not infection is present, so additional testing can be avoided and therapeutic options can be made.

Adult↗
PubMed1997

Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: the role of cytomegalovirus disease.

Epstein-Barr virus (EBV) plays a major role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD). Patients who undergo primary EBV infection after transplantation are at greater risk of developing PTLD. In this retrospective study, the incidence of EBV infection and associated PTLD in 40 consecutive adult recipients who were seronegative for EBV at the time of liver transplantation were investigated, and risk factors for PTLD were analyzed. Of 37 patients with available timely posttransplant serum samples, 35 (95%) developed primary EBV infection. Of the 40 patients, 13 (33%) developed PTLD a median of 126 days (range, 48-776) after liver transplantation. The factor significantly associated with the development of PTLD was cytomegalovirus disease (relative risk, 7.3; 95% confidence interval, 2.36-22.6; P = .0006). Cytomegalovirus disease is a predictor for the development of PTLD in primary EBV infection after liver transplantation, and it may be a target for prophylactic intervention.

Adult↗
PubMed1997

Utilization and diagnostic yield of blood cultures in a surgical intensive care unit.

OBJECTIVE: To evaluate the diagnostic yield of blood cultures obtained in a surgical intensive care unit (ICU) and to assess factors potentially influencing yield. DESIGN: Retrospective, descriptive study. SETTING: Surgical ICU in a university hospital. SUBJECTS: All patients who had a blood culture obtained during their admission to the trauma/neurosurgical ICU of Presbyterian University Hospital from January 1, 1993 to December 31, 1993. MEASUREMENTS AND MAIN RESULTS: Blood culture isolates were categorized as pathogens or contaminants and overall diagnostic yield was determined. Blood cultures were positive for pathogens in 4.6% of all culture episodes, while contaminants were isolated in 5.5% of all culture episodes. A total of 23 true bacteremias were identified in 21 patients, for an overall rate of bacteremia of 3.6 per 100 admissions (5.9 per 1,000 patient days). Concurrent antibiotics were being used at the time of blood culture in 65.3% of all culture episodes. The yield for pathogens was significantly lower (2.2%) when cultures were obtained on antibiotics compared with culture episodes obtained off antibiotics (6.4%) (p < .05). Single-set blood culture episodes were obtained in approximately 32% of all culturing episodes with the overall yield for pathogens of these culturing episodes lower (2.9%) than that of multiple-set culture episodes (5.3%) (p = NS). CONCLUSIONS: Blood culture yield in this surgical ICU was relatively low in comparison with other published studies. The data further suggest that concurrent use of systemic antibiotics and inappropriate or excessive culturing may negatively influence blood culture yield.

Bacteremia↗
PubMed1996

In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor/vascular endothelial growth factor.

To investigate the in vivo angiogenic activity of placenta growth factor (PIGF) and its heterodimers with vascular endothelial growth factor (VEGF), the induction of neovascularization of these factors in the mouse cornea was studied. VEGF165 is sufficiently potent to stimulate new capillary growth from the limbal vessels. PIGF129/VEGF165 heterodimers also induce corneal neovascularization with a maximal vessel length similar to VEGF165, but with a marked decrease of vessel density. In contrast, PIGF129 has little or no effect in this in vivo angiogenesis assay. The expression of VEGF mRNA and protein is drastically up-regulated by hypoxia in choriocarcinoma cells, whereas expression of PIGF is not affected by the low concentration of oxygen. Up-regulation of VEGF production results in increased formation of PIGF/VEGF heterodimers in these tumor cells. Thus, hypoxia indirectly up-regulates expression levels of PIGF/VEGF heterodimers and modulates VEGF activity when these factors are co-expressed.

Angiogenesis Inducing Agents↗
PubMed1996

Factors associated with the development of candidemia and candidemia-related death among liver transplant recipients.

OBJECTIVE: The authors' objective was to identify factors associated with candidemia and candidemia-related death among adult liver transplant recipients. SUMMARY BACKGROUND DATA: Invasive candidiasis is the most common severe fungal infection occurring after liver transplantation and is associated with high morbidity and mortality rates. Although candidemia is not always found during invasive candidiasis, it has been considered as an indicator of invasive candidiasis in immunocompromised patients. METHODS: A time-matched case-control study of 26 patients with candidemia, which was defined as the isolation of Candida from at least one blood culture, and 52 control patients without candidemia was reported. Two control patients were matched with each case patient regarding time of transplantation and duration of follow-up. RESULTS: Between December 1985 and December 1992, candidemia developed in 1.4% of adult liver transplant recipients a median of 25 days after transplantation (range, 2-1690 days). The overall mortality rate among patients with candidemia was 81%, and 71% of these deaths were related to candidemia. Conditional logistic regression analysis was used to identify factors associated with candidemia, which were 1) hyperglycemia treated with insulin up to 2 weeks before candidemia (odds ratio [OR], 16.15; p = 0.002), and 2) exposure to more than three different intravenous antibiotics before development of candidemia (OR, 11.15; p = 0.005). The variables predictive of death related to candidemia were abdominal surgery performed up to 1 week before candidemia (relative risk [RR], 7.25; p = 0.02), high white blood cell count (RR, 1.10; p = 0.01), lower platelet count (RR, 0.99; p = 0.02), and elevated AST with candidemia (RR, 1.001; p = 0.01). CONCLUSIONS: Hyperglycemia that requires insulin and exposure to more than three antibiotics are the factors associated with the development of candidemia in liver transplant recipients. When candidemia develops shortly after abdominal surgery and in patients with elevated AST, high white blood cell count, or low platelet count, it is associated with a high mortality rate.

Adult↗
PubMed1994

A prospective randomized trial comparing sequential ganciclovir-high dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease in adult liver transplant recipients.

Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; P < 0.00001). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P = 0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P = 0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P = 0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population.

Acyclovir↗
PubMed1994

Successful therapy for cerebral phaeohyphomycosis due to Dactylaria gallopava in a liver transplant recipient.

A 68-year-old liver transplant recipient who was being treated with FK 506 and immunosuppressive steroid therapy was admitted to our medical center because of a tonic-clonic seizure. Computed tomography of the head revealed multiple discrete cerebral abscesses, and culture of fluid drained intraoperatively yielded a dematiaceous fungus. The isolate was susceptible to amphotericin B and itraconazole but was resistant to flucytosine and fluconazole. The patient was successfully treated with a prolonged course of amphotericin B colloidal dispersion and itraconazole, as evidenced by both clinical and radiographic resolution of disease over a 2-year follow-up.

Aged↗