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G J Locker

Publications and source records attributed to G J Locker.

At least 19 recordsLinked to original sources
PubMed2000

Benefit of interferon-alpha2b in a patient with unresectable hepatoma and chronic infection with hepatitis C virus.

Only in a small proportion of patients is advanced hepatocellular carcinoma (HCC) resectable, so the need for effective non-surgical treatments is obvious. We present details of a 72-year-old woman with inoperable HCC and chronic infection with hepatitis C virus, proved by the presence of antibodies directed against hepatitis C virus and positive polymerase chain reaction. The patient was treated with subcutaneous recombinant human interferon-alpha-2b. Within a few weeks, a partial tumour remission, paralleled by a decrease in serum levels of tumour markers and liver enzymes, was observed. In addition, polymerase chain reaction became negative. This observation facilitates the hypothesis that the anti-viral effects of interferon might have been jointly responsible for the anti-tumour activity observed. Interferon-alpha might serve as a treatment option in patients with unresectable hepatoma and chronic active viral hepatitis, but prospective studies are warranted.

Aged↗
PubMed2000

Homocysteine and laminin are not prognostic markers in patients with septic inflammatory response syndrome.

The aim of this study was to measure plasma homocysteine and laminin concentrations in patients with nonbacteremic systemic inflammatory response syndrome (SIRS) and to compare them with those of a healthy control group. Concerning laminin, significant increased concentrations could be observed in the SIRS group compared to the control group, but for homocysteine, no significance could be observed. In summary, homocysteine and laminin levels are not useful in the prediction of a patient's outcome.

Adult↗
PubMed1999

[Clinical phase II-evaluation of neoadjuvant, cytostatic combination chemotherapy with docetaxel and epidoxorubicin in female breast cancer patients (T1-4, N0-2, M0)].

BACKGROUND: Preoperative (neo-adjuvant) chemotherapy is very effective in downstaging primary tumors and moreover is able to prevent advancing metastatic growth early in the course of the disease. METHODS: We report on 38 patients with a median age of 54 years (range, 33-70 years) suffering from biopsy-proven breast cancer (T1-T4). Mastectomy had been considered the treatment of choice in all cases. The patients received 194 cycles of chemotherapy with docetaxel (75 mg/m2) and epidoxorubicin (75 mg/m2) on day 1, every 21 days, together with 30 million IU of G-CSF from days 3 to 10. Three to 8 cycles (median 5 cycles) of the treatment were administered until best response was achieved on mammography and clinical assessment. RESULTS: The neo-adjuvant chemotherapy was well tolerated and all patients completed the treatment regimen on an out-patient basis. During 194 cycles we observed leukopenia WHO grade IV only at one occasion (0.5%). WHO-grade III toxicity consisted of leukopenia (0.5%), diarrhoea (2%), and stomatitis (0.5%). Response to treatment was present in 85%, with 4 patients (11%) experiencing a pathological complete response (pCR) of the invasive tumor (T0: n = 2, DCIS: n = 2) and 28 patients (74%) showing a partial pathological response. In 21 patients (52%) a breast-conserving surgical procedure was possible. SUMMARY: We conclude that neo-adjuvant treatment of primary breast cancer with docetaxel and epidoxorubicin is safe and effective. By applying more chemotherapy cycles preoperatively it might even be possible to raise the rate of pCR and prolong survival.

Adult↗
PubMed1999

Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients.

OBJECTIVE: To evaluate thrombogenicity of prothrombin complex concentrates (PCCs) in critically ill patients. DESIGN: Prospective clinical study. SETTING: Medical intensive care unit at a university hospital. PATIENTS: 16 consecutive patients suffering from acquired deficiencies of coagulation factors and with either overt bleeding from any site or a planned invasive procedure. INTERVENTIONS: 2000 factor IX units of PCCs intravenously. MEASUREMENTS AND RESULTS: Prothrombin time (PT), activated partial prothrombin time, fibrinogen, platelet count, plasma levels of coagulation factors II, V, VII, VIII, IX, X, antithrombin, protein C, thrombin-antithrombin complex (TAT), prothrombin fragment F(1+2), and the fibrin degradation product D-dimer were measured prior to and 1, 3, and 24 h after administration of PCCs. PT as well as coagulation factors II, VII, IX, and X, TAT, and F(1+2) showed a significant increase after administration of PCCs. All other parameters remained unchanged. CONCLUSIONS: Administration of PCCs induces thrombin generation. No evidence for induction of disseminated intravascular coagulation in biochemical terms could be found. When rapid correction of acquired coagulation factor disturbances is warranted, the use of PCCs seems reasonable, but the elevated risk of intravascular thrombus formation should be kept in mind.

Adult↗
PubMed1999

Placement of a pulmonary artery catheter via a previously unrecognized persistent left superior vena cava.

This case report describes a patient with persistent left superior vena cava (LSVC) as discovered by difficult placement of a pulmonary artery catheter via the left subclavian vein. After positioning in wedge position, chest x-ray showed a catheter route suggestive of persistent LSVC. Since this abnormality may yield potential clinical complications, this possibility should be considered in every difficult central venous access.

Adult↗
PubMed1999

Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders.

Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL-2-based side-effects. In nine tumour patients receiving intravenous rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) and the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P<0.05), indicating activation of endothelial cells. The simultaneous increase of tissue-plasminogen activator and plasminogen activator inhibitor type-1 during therapy (P<0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P<0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET-1 might act as an endogenous counter-regulator of the disadvantageous haemodynamic side-effects induced by IL-2.

Blood Coagulation↗
PubMed1999

Continuous infusion versus intermittent administration of meropenem in critically ill patients.

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

Adolescent↗
PubMed1999

Use of abciximab-modified thrombelastography in patients undergoing cardiac surgery.

UNLABELLED: Thrombelastography (TEG) is a reliable coagulation monitoring system that can guide blood product transfusion in cardiac surgery. The maximum amplitude (MA) of TEG measures clot strength, which is dependent on both fibrinogen level and platelet function. Inhibition of platelet function with abciximab-fab is suggested to permit quantitative assessment of the contribution of fibrinogen to clot strength. We hypothesized that abciximab-modified TEG permits prediction of plasma fibrinogen levels and that the difference of standard MA and abciximab-modified MA (deltaMA) is a correlate for platelet function. We correlated abciximab-modified MA with plasma fibrinogen levels and deltaMA with platelet count in patients undergoing coronary revascularization. Correlation between plasma fibrinogen levels and abciximab-modified MA was significant (adjusted r2: 0.8; P < 0.0001). Correlation of deltaMA with platelet count was not significant when calculated in millimeters (adjusted r2: 0.04; P = 0.73). However, when deltaMA was calculated in dynes per square centimeter (deltaGMA), it correlated significantly with platelet count (adjusted r2: 0.51; P < 0.0001). We conclude that abciximab-modified TEG may therefore help to discriminate between hypofibrinogenemia and platelet dysfunction as a cause of decreased MA. IMPLICATIONS: We examined the use of abciximab-modified thrombelastography in patients undergoing cardiac surgery. Modification of thrombelastography with abciximab-fab allows prediction of fibrinogen levels, despite coagulation altered by cardiac surgery. The difference of standard maximum amplitude and abciximab-modified maximum amplitude correlates with platelet function when expressed in dynes per square centimeter.

Abciximab↗
PubMed1999

Induction of immunomediated diseases by recombinant human granulocyte-macrophage colony-stimulating factor during cancer treatment?

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is widely used in the treatment or prevention of neutropenia induced by cytostatic regimens. Recent studies with this cytokine have shown several local and/or systemic side effects. We herein report on four patients with different tumor entities receiving GM-CSF as a part of their intensified cytostatic regimen. All four patients developed immune phenomena (sicca syndrome, seropositive arthralgia, hyperthyroidism, and pneumonitis, respectively) during or after subcutaneous treatment with GM-CSF. Pathologic alterations in immunologic serum parameters as well as histopathologic findings accompanied the clinical symptoms. These observations suggest that the therapeutic application of GM-CSF might be involved in the clinical emergence of autoimmune diseases.

Adult↗
PubMed1999

Negative chronotropic effects of fentanyl attenuate beneficial effects of dobutamine on oxygen metabolism: hemodynamic and pharmacokinetic interactions.

Opioids are well known to cause cardiovascular depression. The aim of the present investigation was to determine whether an interaction of opioid derivatives with catecholamines might be involved in these hemodynamic alterations. Six comatose patients were enrolled into a prospective, nonrandomized pilot trial. All patients first received a continuous i.v. infusion of dobutamine (10 microgram. kg-1. min-1) paralleled by continuous administration of midazolam (0.4 mg. kg-1. h-1); thereafter, fentanyl was added i.v. (4 microgram. kg-1. h-1). Hemodynamic parameters as well as dobutamine and endogenous catecholamines plasma levels were determined. The mean arterial blood pressure did not change significantly during the whole study period. The continuous administration of dobutamine (steady-state plasma concentrations: 217 +/- 118 ng. ml-1) increased the beta1-adrenergic receptor-mediated hemodynamic parameters such as heart rate, stroke volume index, cardiac index, and oxygen delivery index (p <.05). The concomitant administration of fentanyl decreased the heart rate-dependent hemodynamic parameters (p <.05), suggesting that fentanyl antagonizes the chronotropic effects of dobutamine. In parallel, dobutamine plasma levels increased significantly (275 +/- 165 ng. ml-1; p <.05). Noteworthy, after administration of fentanyl, oxygen delivery and consumption index returned to baseline values. Radioligand binding experiments on rat cardiac ventricular microsomes ruled out a direct interaction of fentanyl with beta-adrenergic receptors and, more importantly, a fentanyl-induced inhibition of beta-adrenergic receptor G protein coupling. Our observations suggest that fentanyl inhibits the frequency-related hemodynamic changes induced by dobutamine. The underlying mechanism is independent of beta-adrenergic receptors, but is powerful enough to abolish the salutary effect of dobutamine on oxygen delivery and consumption.

Aged↗
PubMed1998

Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis.

The aim of the present study was to evaluate the potential prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11 patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by isolation of at least two positive blood cultures with gram-positive/gram-negative bacteria. Plasma samples for determination of the immunological parameters were collected daily. Analysis of cytokines and adhesion molecules was performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day before death). In the gram-positive group 10 of 28 patients died; in the gram-negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be a useful early parameter in predicting patients' outcome in gram-positive sepsis. sELAM-1 concentrations at the onset of the study (day 0) were significantly higher in the nonsurviving patients than those in the survivors. MIP-1 alpha levels were significantly higher only on days 4 and 7. With regard to the measured plasma concentrations we believe that MIP-1 alpha is not a useful parameter for predicting patients' prognosis. The increase of sVCAM-1 might play a role in the pathogenesis of gram-positive sepsis; however, it could not be relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in the development of gram-positive sepsis could not evaluated in the present study, whereas routine measurements of TGF-beta 2 offered no additional prognostic information.

Adult↗
PubMed1998

Assessment of the proper depth of endotracheal tube placement with the Trachlight.

STUDY OBJECTIVE: To test the hypothesis that the correct depth of the endotracheal tube can be confirmed by transillumination method using the Trachlight device, which is a newly introduced lighted stylet for guided, blind tracheal intubation. DESIGN: Prospective, nonrandomized pilot-trial. SETTING: University-affiliated hospital. PATIENTS: 72 intubated and mechanically ventilated critically ill adult patients. INTERVENTIONS: Patients were briefly disconnected from the respirator. The centimeter marks of the Trachlight cather were brought into line with those of the endotracheal tube, resulting in congruence of the bulb of the Trachlight and the tube tip. MEASUREMENTS AND MAIN RESULTS: To measure the distance from the tip of the tube to that of the sternal notch, the Trachlight wand was retracted without moving the endotracheal tube until the bright light appeared in the sternal notch. A chest radiograph was taken to measure the distance between the carina and the tip of the tube. The Trachlight showed a distance of 4.0 +/- 1.3 cm from the tip of the tube to the sternal notch. Chest radiography revealed a distance of 3.3 +/- 1.6 cm between the carina and the tip of the tube, so that the calculated distance between sternal notch and carina was 7.3 +/- 1.5 cm. CONCLUSION: To achieve proper depth of the endotracheal tube, it is recommended that the tip of the endotracheal tube be placed 3 cm beyond the sternal notch. The Trachlight provides a simple and easy technique to achieve this goal.

Adult↗
PubMed1998

Time course of immunological markers in patients with the systemic inflammatory response syndrome: evaluation of sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and TGF-beta 2.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) is viewed as a system-wide inflammatory response. Up until now, no parameter has been available for predicting the development of septic shock. In the present study, we evaluated the usefulness of serum levels of CD14, vascular cells adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), macrophage inflammatory protein (MIP) 1 alpha and transforming growth factor beta 2 (TGF-beta 2) as early markers of outcome in patients with SIRS. METHODS: A group of 28 SIRS patients (13 survivors/15 non-survivors) was compared with a healthy control group and with patients with local inflammation. Blood samples were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and anti-inflammatory parameters such as TGF-beta 2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: At the beginning, all evaluated proinflammatory immunological parameters with the exception of sVCAM-1 were significantly increased in patients with SIRS compared with the healthy control group. However, no significant difference could be observed for all immunological parameters comparing survivors and non-survivors, with the exception of interleukin (IL) 6 at day 7. CONCLUSION: All evaluated proinflammatory parameters were increased in patients with SIRS during the course of the disease. However, the parameters have no correlation with outcome and prognosis of SIRS patients.

Adult↗
PubMed1998

Comparison of oxygen cost of breathing with pressure-support ventilation and biphasic intermittent positive airway pressure ventilation.

OBJECTIVE: To assess the oxygen cost of breathing with either pressure-support ventilation (PSV) or biphasic intermittent positive airway pressure ventilation (BIPAP). DESIGN: Prospective, randomized, crossover study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Twenty clinically stable and spontaneously breathing patients after long-term mechanical ventilation. INTERVENTIONS: Patients were randomized to start on either PSV or BIPAP, and measurements were performed after an adaptation period of 30 mins. Immediately after, the ventilatory mode was changed and after another 30-min adaptation period, the same measurements were performed. MEASUREMENTS AND MAIN RESULTS: Indirect calorimetry was performed during each ventilatory mode for a period of 30 mins. Oxygen consumption, energy expenditure, CO2 production, and respiratory quotient did not differ significantly between the two ventilatory modes, regardless of the patients' randomization. There were no statistically significant differences with regard to respiratory rate, minute volume, and blood gas analysis. All patients tolerated both ventilatory modes without any signs of discomfort. CONCLUSIONS: Pressure support ventilation and BIPAP are both used for weaning patients gradually from the ventilator. BIPAP may be advantageous in patients not breathing sufficiently with PSV, since no patient effort is necessary with use of this ventilatory mode.

Adult↗
PubMed1998

Diagnostic validity of pulmonary artery catheterization for residents at an intensive care unit.

OBJECTIVE: To assess the amount of additional information provided by measurements derived from pulmonary artery catheter (PAC) use beyond that derived from clinical evaluation by intensive care residents. METHODS: One hundred forty-nine consecutive patients undergoing right-heart catheterization were prospectively included in the study. Before inserting a PAC, physicians had to predict pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), cardiac index (CI), mixed venous oxygen saturation (SvO2), oxygen delivery (DO2), oxygen consumption (VO2), and pulmonary shunt fraction (Qs/Qt) by selecting a given option on a questionnaire. Ranges of options were chosen to create clear clinical differences among them. RESULTS: The correct value was predicted in a median of 50% of cases (range, 45-63%). PAP was predicted correctly in 55%, PCWP in 46%, SVRI in 63%, CI in 62%, SvO2 in 45%, DO2 in 45%, VO2 in 51%, and Qs/Qt in 51%. A significant difference was found between estimated and measured values for all parameters (p < 0.01). No significant differences were detected between more and less experienced physicians. There was no significant difference between estimated and measured values with respect to the different courses of intensive care unit admissions or the different indications for PAC insertion. CONCLUSION: In a selected group of critically ill patients, the PAC adds valuable and clinically relevant information to clinical assessment in about 50% of cases. Its use should not be withheld in patients with unclear hemodynamic and metabolic profiles.

Catheterization, Swan-Ganz↗
PubMed1998

[Experiences with inhalative nitric oxide in internal medicine intensive care patients with adult respiratory distress syndrome].

Inhalative nitric oxide (NO) has recently been included in the therapeutic armament for the treatment of ARDS. We evaluated the effect of inhalative NO on hemodynamic and oxygen transport parameters in 30 internal intensive care patients suffering from ARDS. All patients received a pulmonary artery catheter. Hemodynamics were assessed prior to NO therapy and after 1, 6, 12, and 24 h. 80% (n = 24) of the patients were classified as therapy responders. The median NO dose was 15 ppm (range 5 to 40 ppm). The PaO2/FiO2--ratio increased significantly after initiation of NO (p = 0.0002) while the pulmonary shunt fraction (Qs/Qt) decreased significantly (p = 0.0019). All other measured or calculated parameters including arterial and pulmonary arterial blood pressure remained unchanged. No negative effects of the therapy could be observed. Inhalative NO improves oxygenation in most intensive care patients with ARDS and thus offers the possibility to reduce invasiveness of mechanical ventilation.

Administration, Inhalation↗
PubMed1997

Renal tolerability of four different once-daily dose regimen of netilmicin in critical care patients.

A prospective, randomized trial was conducted in a medical intensive care unit to assess safety and tolerability of four different dose regimens of intravenous netilmicin given once daily in the treatment of febrile episodes in critically ill patients. Eighty patients with febrile episodes during their stay in the intensive care unit were included in the study. The patients were randomized into four groups: Group 1 received a single daily dose of netilmicin based upon weight, age and renal function according to a dosage nomogram [13] (mean dose 298 +/- 29 mg, median 300 mg, range 250-350 mg), group 2 received 150% of this standard dose (mean 418 +/- 45 mg, median 400 mg, range 350-500 mg), group 3 200% (mean 525 +/- 41 mg, median 500 mg, range 400-550 mg) and group 4 250% (mean 710 +/- 39 mg, median 650 mg, range 600-750 mg). Duration of treatment was six days. Positive cultures were obtained in 29 patients. Serum creatinine and creatinine clearance, as well as netilmicin trough levels and levels of alpha 1-microglobulin showed no significant difference between the groups before, during, and after therapy. Our results indicate that with once daily dosing even high doses of netilmicin are well tolerated in patients with a creatinine clearance of > 70 ml/min before therapy. Necessary precautions include monitoring of drug trough levels (< 1 mg/L) and maintenance of adequate volume status.

Acute Kidney Injury↗