Search PubMed⌕ Search

Biomedical subjects

G J Locker

Publications and source records attributed to G J Locker.

53 records · Page 3Linked to original sources
PubMed1997

Prostaglandin E1 inhibits platelet decrease after massive blood transfusions during major surgery: influence on coagulation cascade?

BACKGROUND: A plunge in platelet count if often observed after massive blood transfusions during major surgery. This study was designed to assess whether the prophylactic administration of prostaglandin E1 (PGE1) might prevent this drop in platelet count. METHODS: Forty-five patients receiving massive transfusions of packed red blood cells (> 10 units) during major orthopedic surgery were enrolled in a prospective, randomized, double-blind, placebo-controlled study and divided into two groups: group 1 (therapy group) received intravenous PGE1 up to 30 ng/kg/min for 72 hours after surgery, and group 2 (placebo group) received a placebo during the same time period. RESULTS: The patients in group 1 suffered no reduction in platelet count and thus required no platelet concentrate transfusions. In contrast, a significant postoperative drop in platelet count (p < 0.05) was observed in the placebo group between days 3 and 5 after surgery when compared to the therapy group, necessitating transfusions of platelet concentrates in this group. Similarly, red blood cell count and hemoglobin were far more stable in the therapy group, which required fewer transfusions of red blood cells than did the placebo group (p < 0.05). There seemed to be a tendency toward a consumptive coagulation disorder in the placebo group as indicated by a decrease of fibrinogen levels, prothrombin time, and antithrombin III activity, and an increase of partial thromboplastin time. The incidence of adult respiratory distress syndrome was slightly lower in the therapy group. Last but not least, the length of intensive care unit stay was significantly shorter in the therapy group (p < 0.05). CONCLUSION: In our study, the administration of PGE1 prevented a reduction in platelet count. Furthermore, measurements of clotting activity furnished the possibility that PGE1 might inhibit transfusion-induced coagulation disturbances. We recommend that PGE1 should be considered in patients requiring massive transfusion during major surgery.

Adult↗
PubMed1996

Increased serum concentration of soluble CD14 is a prognostic marker in gram-positive sepsis.

Increased serum sCD14 concentrations are associated with poor outcome in Gram-negative sepsis and trauma patients. In the present study serum sCD14 concentrations were measured in patients with Gram-positive sepsis and compared with Gram-negative septic and nonseptic intensive care unit patients. Furthermore, serum sCD14 concentration was correlated with patient's outcome. Serum samples of 28 Gram-positive (8 nonsurvivors/20 survivors) and 10 Gram-negative bacteriemic patients (3 nonsurvivors/7 survivors) were obtained at the day they met the sepsis criteria defined by Bone et al. (Day 0) and at Days 4 and 7 and compared with 10 nonseptic ICU patients and 10 healthy volunteers. Serum concentrations of sCD14 were measured by ELISA. Significantly higher sCD14 serum concentrations were found on Days 4 and 7 in Gram-positive nonsurvivors than in Gram-positive survivors (Day 4: 5.85 +/- 0.48 vs 4.07 +/- 0.43 microgram/ml, P < 0.05; Day 7: 6.12 +/- 0.46 vs 3.53 +/- 0.33 microgram/ml, P < 0.01). In addition, sCD14 concentrations of Gram-positive nonsurvivors were significantly higher than those of nonseptic ICU patients and healthy volunteers at any time of observation. However, no significant difference was calculated between Gram-positive and Gram-negative patients. Summarizing our results, the serum level of sCD14 could be proven to be a good prognostic marker in the course of Gram-positive sepsis. Increased levels are associated with a high mortality.

Adult↗
PubMed1996

Influence of pentoxifylline on cytokine levels and inflammatory parameters in septic shock.

OBJECTIVE: To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock. DESIGN: Prospective study comparing a therapy group to a matched control group. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group. INTERVENTIONS: Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group. MEASUREMENTS AND RESULTS: Cytokine levels [tumor necrosis factor-alpha (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, alpha-1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h-later. After 24 h, TNF levels were significantly lower in the therapy group (p = 0.013), while IL-6 levels were significantly higher in the therapy group (p = 0.030). Within the 24 h TNF declined significantly in the therapy group (p = 0.006), while IL-6 showed a significant increase (p = 0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p = 0.05), APACHE III score lower (p = 0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p = 0.0026) whereas the cardiac index declined (p = 0.035). CONCLUSIONS: PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.

APACHE↗
PubMed1996

Management of acquired coagulation disorders in emergency and intensive-care medicine.

Coagulation disorders usually confront the emergency physician as bleeding episodes or as abnormalities of laboratory tests. Bleeding has to be treated aggressively, while pathological coagulation tests should be related to a more differentiated diagnosis at first. The most common causes of acquired coagulation disorders are liver disease, vitamin K deficiency, and disseminated intravascular coagulation (DIC). More rarely, inhibitors, external factors such as drugs or extracorporeal circulation, or other diseases such as amyloidosis are present. Since localized hemorrhage is the most common bleeding source in liver disease, endoscopic and surgical therapeutic measures, respectively, are warranted. Careful and balanced substitution therapy according to laboratory findings should be initiated simultaneously and should consist of fresh frozen plasma (FFP), which contains all components of the coagulation system physiologically balanced. Prothrombin complex concentrates should be used in emergency situations only, keeping their potential hazards in mind. Adequate vitamin K substitution is indicated in liver disease as well as in coagulopathy due to vitamin K deficiency. Management of DIC primarily consists of aggressive treatment of the underlying disease. Substitution therapy is difficult and should be carefully monitored by the adequate laboratory tests. FFP is the adequate source of both procoagulants and inhibitors but may cause certain problems. Heparin therapy can be beneficial but is not recommended generally. Antithrombin III substitution cannot be assumed as established therapy so far. Inhibitors can lead to bleeding, but the most common inhibitor, lupus anticoagulant, rather predisposes to thrombosis. In bleeding patients with inhibitors against single clotting factors, treatment consists of adequate substitution before initiating the diagnostic workup.

Anticoagulants↗
PubMed1996

[Results of critical care management of patients after bone marrow transplantation].

In a retrospective study we investigated the clinical course of patients who required intensive care support after bone marrow transplantation. Out of 25 patients only 5 (20%) survived treatment in the intensive care unit (ICU) and this group showed a significantly lower age, lower APACHE III and organ-failure scores and higher serum albumin values, as well as a longer interval between bone marrow transplantation and admission to intensive care. However, no patient requiring mechanical ventilation primarily for pneumonia or other infections arising as a complication of bone marrow transplantation survived intensive care. All patients requiring ventilation for more than 24 hours died in hospital. Of the 5 patients surviving ICU treatment only 3 were eventually discharged from hospital and only one single patient was alive after 6 months. Hence, current intensive care management appears to be indicated in only a small group of patients after bone marrow transplantation.

APACHE↗
PubMed1995

Cutaneous side effects in breast cancer patients treated with cytostatic polychemotherapy and rh GM-CSF: immune phenomena or drug toxicity?

The application of recombinant colony stimulating factors for chemotherapy induced granulocytopenia is becoming common in clinical oncology. Here we report on localized cutaneous side effects after subcutaneous administration of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) in 11 patients with breast cancer receiving cytostatic treatment. Seven patients suffering from inflammatory breast cancer received cytostatic chemotherapy with mitoxantrone/cyclophosphamide, whereas four patients suffering from noninflammatory breast cancer received high-dose epirubicin/cyclophosphamide, respectively. rh GM-CSF was applicated subcutaneously in a dose of 5 micrograms/kg/d for at least ten days. In all patients, sharply demarked, maculous itching and burning erythemas restricted to the injection sites occurred after three to four injections of rh GM-CSF. These eruptions cleared within 2 to 3 weeks, but reappeared after reexposure to rh GM-CSF. In contrast to previous sporadic reports, no generalized erythemas were observed. Because of this unexpected and subjectively intolerable side effect, rh GM-CSF administration had to be interrupted in all patients. Histopathological findings revealed skin infiltration with lymphocytes, monocytes/macrophages, neutrophils, and occasionally eosinophils, respectively. Since GM-CSF is known to alter immune functions, it seems likely that the eruptions were at least in part due to local immune reactions.

Adenocarcinoma↗
PubMed1995

Factitious hyperthyroidism causing acute myocardial infarction.

Myocardial ischemia is a rare but severe and possibly life threatening manifestation of hyperthyroidism, but does not usually result in persistent ischemia. We report on a 71-year-old woman who had undergone total thyroidectomy with subsequent irradiation because of follicular carcinoma 3 years ago. Since then, she had been maintained on oral levothyroxine replacement therapy at a dose of 0.15 mg alternating with 0.2 mg daily. When latent hypothyroidism became evident despite replacement therapy, the dose of levothyroxine was increased to 0.3 mg a day. Three weeks later, the patient suffered from an acute posterior myocardial infarction, although she had no previous history of coronary artery disease. Subsequent coronary arteriograms revealed no evidence of disease of the major vessels. Myocardial scintigraphy 3 weeks after infarction still revealed a persistent perfusion defect. Since it is known that thyroid hormones increase oxygen demand, the rapid elevation of oxygen utilization caused by thyrotoxicosis factitia is likely to be responsible for this patient's myocardial infarction. The case illustrates that a sudden increase in levothyroxine replacement dose should be avoided.

Acute Disease↗
PubMed1995

Lethal Waterhouse-Friderichsen syndrome in posttraumatic asplenia.

We herein report a case of fulminant lethal Waterhouse-Friderichsen syndrome in an elderly female patient seven years after posttraumatic splenectomy. In contrast to various reports, this patient had not been vaccinated against Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae, respectively, although infections with these microorganisms are known to cause the main lethal diseases in asplenic patients. Again, we recommend obligatory vaccinations against the mentioned bacteria for it is known that this decreases the risk of fatal septic events in these patients. To optimize prevention, it is imperative to vaccinate patients undergoing splenectomy before discharge from hospital.

Blood Coagulation Tests↗
PubMedDate not supplied

New mucin-like cancer-associated antigens (CA M 26, CA M 29 and CA 549) and a new proliferation marker (TPS) in patients with primary or advanced breast cancer.

In patients with breast cancer no tumor markers giving satisfactory results have been found yet. The aim of our investigation was to compare the usefulness of newly developed tumor markers with the most common used carcinoembryonic antigen and cancer antigen (CA) 15-3. We evaluated the concentrations of carcinoma-associated antigen (CA) 549, carcinoma-associated mucin antigen (CA M) 26 and CA M 29, and the proliferation markers tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS) in 84 breast cancer patients with disease progression and in 69 patients with no evidence of disease after surgery for breast cancer. Using receiver-operating characteristic curves (ROC curves) we were able to demonstrate increased sensitivity and specificity of all tested tumor markers in patients with metastatic disease compared with local disease. In our investigation TPA is superior to TPS in all disease states. In local disease, none of the tested markers shows satisfying results. In metastatic disease, the new mucin markers CA M 26 and CA M 29 show slightly better results than CA 15-3 although their ROC curves are nearly congruent. CA 549 is exceeded by the other mucin markers. The best results in this investigation were obtained with CA M 29. The overall results concerning the detection of small tumor masses (i.e. local disease) were unsatisfactory.

Adult↗
PubMedDate not supplied

Sequential administration of interferon-gamma, GM-CSF, and interleukin-2 in patients with metastatic renal cell carcinoma: results of a phase II trial.

Various cytokine combinations have been tested for efficacy in the treatment of metastatic renal cell carcinoma (MRCC). Because several immunologic synergisms between granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been demonstrated, this phase II trial was conducted on the efficacy and toxicity of subcutaneous, sequentially administered, interferon-gamma (IFNgamma), GM-CSF, and IL-2. Fifty-five consecutive patients with MRCC were treated with 100 microg recombinant IFNgamma1b administered thrice weekly during weeks 1 and 4, followed by 400 microg GM-CSF on 5 consecutive days during weeks 2 and 5. In weeks 3 and 6, patients received 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was repeated every 8 weeks. Five (10%) of patients experienced an objective response (complete response [CR]: 2%, partial response [PR]: 8%). Fourteen (26%) patients had stable disease with a median duration of 19 months (6-47+). The median overall survival was 12 months (range: 0.3-44 months). No toxicity greater than World Health Organization grade II was observed, with fever (43%) and erythema (43%) being the most frequent side effects. Compared with other phase II trials with IFN-gamma and IL-2 alone, the addition of GM-CSF failed to improve response or survival in patients with MRCC.

Adult↗