Biomedical subjects

M W Wichmann

Publications and source records attributed to M W Wichmann.

At least 19 recordsLinked to original sources

PubMed2001

[Laparoscopic splenectomy in thrombotic thrombocytopenic purpura. Surgical and hematological results in 2 patients].

HISTORY: Case 1. Thrombotic-thrombocytopenic purpura (TTP, Moschkowitz' disease) in a 57-year-old woman had for one year been treated conservatively. But when daily plasmapheresis was temporarily discontinued she developed behavioural changes and impaired speech, providing an indication for splenectomy. Case 2. A 53-year-old woman with TTP had been similarly treated for one month. Splenectomy was indicated when neurological symptoms rapidly developed. INVESTIGATIONS: At admission, creatinine 110 mg/d, white cell count (WBC) 12.4 G/l haemoglobin 10.1 g/dl, haematocrit 0.29, platelets 91 G/l. Prothrombin time (PTT) and thromboplastin time were normal. Patient 2. At admission, platelet count was below 10 G/l and she had various neurological abnormalities. Haemoglobin was 9.0 f/dl, haematocrit 0.27. Platelet count, PTT, thromboplastin time and renal functions were normal. TREATMENT AND COURSE: Case 1. After plasmapheresis and administration of cryoprecipitate-free fresh frozen plasma (FFP) excess, laparoscopic splenectomy was performed. On the third postoperative day WBC count was 11.5 G/l, haemoglobin level was unchanged, but platelet count was now normal, as were PTT and thromboplastin time and renal functions. 8 and 32 months after the operation WBC count, haemoglobin, haematocrit and platelets were all normal. There were no neurological abnormalities postoperatively. Case 2. Laparoscopic splenectomy was performed after intensive haematological preparation. The pre- and postoperative course was uneventful and she was discharged on the 8th postoperative day, at which time her haemoglobin was 8.4 g/dl, haematocrit 0.25, while platelets, PTT, thromboplastin time and renal functions were all normal and remained so at follow-up 11 months later. There have been no neurological symptoms after the splenectomy. CONCLUSION: Laparoscopic splenectomy is a haematologically and surgically safe treatment of TTP and should be considered for all cases of TTP that fail to respond to conservative management.

Female↗

PubMed2001

The acute phase response following implantation of triclosan-bonded vascular prostheses.

OBJECTIVE: Infection of prosthetic material is a major complication of vascular surgery. Therapy for it includes implantation of antimicrobial prostheses bonded with different antimicrobial agents. These agents may, however, induce an acute phase reaction following implantation in the host, thus compromising follow-up of the infection. It is not known whether the antimicrobial agent triclosan induces a significant acute phase reaction when bonded to vascular prostheses. METHODS: To study this, 34 adult swine weighing 20-30 kg were allotted randomly to the following groups: (1) controls with untreated prostheses, (2) control group with triclosan-bonded prostheses, (3) therapy group with untreated prostheses, local infection with Staphylococcus aureus surgical revision, and exchange with new, untreated prostheses, and (4) therapy group with untreated prostheses, local infection with S. aureus, surgical revision, and exchange with triclosan-bonded prostheses. Serum C-reactive protein (CRP) and haptoglobin values were determined during the 28-day period after surgery. The study was performed at the Institute for Surgical Research of the Ludwig Maximilian University School of Medicine in Munich. RESULTS: Normal ranges of serum CRP and haptoglobin values were 10.7+/-1.4 microg/ml and 2.5+/-0.3 mg/ml, respectively. Following implantation of untreated and triclosan-bonded vascular prostheses, significantly elevated serum CRP and haptoglobin values were observed. No significant differences between results with triclosan-bonded and untreated prostheses were observed in control or treatment groups. No correlation was found between acute phase reaction and the absence or presence of infection. CONCLUSIONS: Triclosan is the only antimicrobial agent that bonds to vascular prosthetic material without the need of a sealant. Our data indicate that vascular prosthesis implantation, whether untreated and triclosan-bonded, results in a significant acute phase reaction. No differences between antimicrobial and untreated prostheses were observed, independently of the absence or presence of infection. The antimicrobial agent itself did not induce a severe acute phase response and may, therefore, be used in patients at risk of infection.

Acute-Phase Proteins↗

PubMed2001

Gender differences in long-term survival of patients with colorectal cancer.

BACKGROUND: Significant differences exist in the immunological response to surgery. This raises the possibility that gender differences exist concerning the outcome after curative colorectal cancer resection. METHODS: To study this hypothesis, a database of patients with colorectal cancer was analysed prospectively. RESULTS: Some 894 patients were included, 500 (55.9 per cent) were men and 394 (44.1 per cent) were women. Median follow-up was 54.5 months for the entire group and 63.3 months for survivors. The mean(s.e.m.) patient age was 65.3(0.4) years (women 66.1(0.6), men 64.7(0.5) years; P < 0.05). Women lived significantly longer after cancer resection than men (57.8(1.5) versus 52.0(1.3) months; P < 0.05, log rank 0.009). Disease-free survival was significantly longer in women than in men (51.6(1.7) versus 46.0(1.4) months; P < 0.05). Subgroup analysis revealed significant gender differences in Union Internacional Contra la Cancrum (UICC) stages I (n = 195, log rank 0.01) and UICC IV (n = 38, log rank 0.021). Survival analysis after rectal cancer resection revealed significant advantages for women (log rank 0.02), while no gender differences were detected when comparing patients after resection for colonic cancer. Moreover, patients older than 50 years (n = 635) showed significant gender-related survival differences (log rank 0.015). CONCLUSION: Significant gender differences following curative rectal cancer resection were observed. In women disease-free and overall survival were significantly longer. Whether or not these gender differences are related to gender-specific immune functions or to other gender-related local or systemic factors remains to be determined.

Age Factors↗

PubMed2001

[Surgical techniques in hepatic resections: Ultrasonic aspirator versus Jet-Cutter. A prospective randomized clinical trial].

AIM OF THE STUDY: For all resection-techniques of liver tissue intra- and post-operative blood-loss remains an important problem. Two novel resection-techniques the ultrasound-aspirator (CUSA) and the water-jet dissector (Jet-Cutter) appear to offer significant advantages regarding this problem. Aim of the present prospective clinical study was the comparison of these dissection techniques. MATERIAL AND METHODS: Prospective randomized study with the end points blood-loss, length of surgery, tissue trauma and long-term survival. FINDINGS: Significant differences between both procedures with Jet-Cutter (n = 31) versus ultrasonic surgical aspirator CUSA (n = 30) were observed regarding length of resection and complete liver ischemia time (Pringle-time). Here significant advantages of the jet-cutter-technique were observed with 28 +/- 11 minutes length of resection versus 46 +/- 19 minutes and 29 +/- 12 minutes Pringle-time versus 39 +/- 16 minutes. Furthermore, significant fewer blood transfusions were required following jet-cutter-resection with a mean of 1.5 blood units vs. 2.5 blood units using the CUSA. No differences were observed regarding postoperative long-term survival. CONCLUSIONS: The jet-cutter-technique is a fast and safe surgical procedure for liver resections and offers an attractive therapeutic alternative for various indications in liver surgery.

Blood Loss, Surgical↗

PubMed2000

Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome.

OBJECTIVE: Laboratory studies demonstrated significant detrimental effects of male sex-steroids (testosterone) on immune functions following hemorrhagic shock and soft-tissue trauma. Moreover, better survival of female mice subjected to severe sepsis was observed when compared to male animals. The aims of the present study were to evaluate whether or not gender differences regarding incidence and mortality of severe sepsis do exist in surgical intensive care patients and to elucidate the influence of patient age on incidence and mortality of severe sepsis/septic shock. DESIGN: Data base review of prospectively collected data from surgical intensive care patients. SETTING: Surgical intensive care unit of the department of surgery of a university hospital. PATIENTS: Prospectively collected data of 4,218 intensive care patients (2,709 male, 1,509 female). RESULTS: Significantly fewer female patients were referred to the intensive care unit (6.6 % vs 10.8 % of all patients; P < 0.05) leading to a significantly smaller proportion of female intensive care patients (35.8% vs 64.2%). No gender differences regarding number of failing organs or surgical procedure (exception vascular surgery) were observed in patients with and without severe sepsis/septic shock, indicating that the patients studied are comparable regarding general health prior to admission to SICU. Among all female patients referred to SICU only 7.6 % developed severe sepsis/septic shock, while 10.4% of all male patients suffered from severe sepsis or septic shock (P < 0.05). This gender difference results from a significantly lower incidence of severe sepsis/ septic shock in female patients between 60 and 79 years. No gender difference regarding mortality rates of severe sepsis/septic shock was observed (men 64.9 %, women 65.5%). CONCLUSIONS: Our results indicate a significantly smaller number of female patients requiring intensive care as well as a significantly lower incidence of severe sepsis/septic shock in female intensive care patients. Mortality from severe sepsis/ septic shock, however, is not affected by gender.

Adolescent↗

PubMed2000

The role of carcinoembryonic antigen for the detection of recurrent disease following curative resection of large-bowel cancer.

BACKGROUND AND AIMS: During recent years, a discussion about cost-effectiveness and importance of follow-up evaluation after curative resection of large-bowel cancer has developed. It is not known whether the determination of carcino-embryonic antigen (CEA) plays a crucial role in the early detection of recurrent disease. PATIENTS/METHODS: We conducted an analysis of the prospective follow-up database of 1321 patients after curative resection of colorectal cancer in our institution between 1990 and 1998 to evaluate the role of CEA in the early detection of recurrent disease. RESULTS: Of the 1321 patients included in our study, 306 developed recurrent disease following curative resection (23.2%). These patients with recurrent disease were divided into: Group I. No pre-operative CEA determination/insufficient follow-up (n=47; 15.4%). Group II. No elevation of CEA with primary cancer (n=156; 51.0%): (IIa) elevation with recurrent disease (n=62); (IIb) no elevation at any time point (n=53); and (IIc) role of CEA not completely elucidated (n=41). Thirteen patients of group II underwent curative relapse surgery (8.3%). Group III. Elevated CEA with primary cancer (n=103; 33.7%): (IlIa) no increase with recurrent disease (n=21); (IIIb) increase with other symptoms of recurrent disease (n=45); and (IIIc) increased values as an early symptom of recurrent disease (n=37). Sixteen patients of group III underwent curative relapse surgery (15.5%). In patients after relapse surgery, recurrent disease developed again after a median time of 12 months (mean 17.9+/-3.8 months). CONCLUSIONS: Our findings indicate that 2.8% of all patients (12.1% of patients with recurrent disease) who underwent curative resection of colorectal cancer profit from follow-up CEA determinations. With careful observation of CEA kinetics, 6.2% (n=82) of all patients or 26.8% of patients with recurrent disease could profit from routine follow-up CEA determinations. In 9.5% of patients with recurrent disease, curative resection of relapse was achieved and these patients remained disease free for a median time of 12 months. Regular CEA measurements remain an important part of routine patient care after curative resection of colorectal cancer.

Adult↗

PubMed2000

Effect of naloxone on immune responses after hemorrhagic shock.

OBJECTIVE: To determine whether naloxone administration after hemorrhagic shock has any beneficial or deleterious effect on immune responses. BACKGROUND DATA: Hemorrhagic shock is known to produce immunodepression in both humans and experimental animals. Although studies suggest that endogenous opioids play a role in immune regulation in adverse circulatory conditions, it remains controversial whether these opioids exert beneficial or detrimental effects on immunity after shock. Moreover, little information is available concerning the effects of opioid receptor blockade using naloxone on cell-mediated immunity and endocrine responses after shock. METHODS: Male C3H/HeN mice (25 g) were bled to and maintained at a mean arterial blood pressure of 35+/-5 mm Hg for 1 hr. The shed blood was then returned along with lactated Ringer's solution (two times the shed blood volume) to provide fluid resuscitation. The animals were randomized to receive either naloxone (1 mg/kg i.v.) or an equal volume of vehicle (saline) after the shed blood was returned, i.e., immediately before crystalloid resuscitation, and were killed at 2 hrs after resuscitation to obtain splenocytes, macrophages (peritoneal and splenic), and blood. MEASUREMENTS AND MAIN RESULTS: Bioassays revealed significantly decreased release of all studied interleukins (interleukins-1, -2, -3, and -6) by peritoneal and splenic macrophages as well as significantly decreased splenocyte proliferative capacity after shock in vehicle-treated mice. Naloxone administration after hemorrhage resulted in either similar or even more decreased levels of interleukin release compared with vehicle-treated hemorrhaged mice. Significantly increased plasma corticosterone concentrations were observed in vehicle-treated animals compared with control animals. Naloxone administration did not have any significant effects on corticosterone plasma concentrations after hemorrhage. CONCLUSIONS: These findings indicate the importance of the endogenous opioid system for the maintenance of immunity in adverse circulatory conditions, i.e., hemorrhage. Although additional studies involving different doses and/or times of naloxone administration may provide different results, the present findings raise the concern that naloxone administration in the traumatized host may have deleterious effects because it decreases peritoneal macrophage and splenic immune functions.

Animals↗

PubMed1999

Immune dysfunction in trauma.

This article documents that all immunomodulation strategies for patients sustaining traumatic injury are still under intense investigation. Although we can speculate that combination strategies may be more beneficial than single-agent immunomodulation approaches, comprehensive clinical studies are required to determine efficacious immune therapy for trauma patients. The only strategy available to clinicians caring for trauma patients is immunonutrition, and this should be strongly considered as a rational approach to improve immune function and reduce septic complications in critically ill or injured patients.

Adjuvants, Immunologic↗

PubMed1998

[Contribution of soft tissue trauma and/or bone fracture to immune suppression after hemorrhagic shock in the animal experiment].

Bone fracture, soft-tissue trauma and hemorrhagic shock are frequent complications in trauma patients, and these patients are known to be immunocompromised. Nonetheless, it is difficult to differentiate the effect of soft-tissue trauma plus hemorrhage from that of bone fracture and hemorrhage on host immune function in the clinical setting. To determine this experimentally, closed bone fracture (right lower leg) and/or soft-tissue trauma (2.5 cm midline laparotomy) were induced prior to hemorrhagic shock (mean arterial BP of 35 +/- 5 mm Hg for 90 min) in male C3H/HeN mice. All animals were killed at 72 h after initiation of the experiment and the spleens were collected aseptically. More significant depression of splenocyte IL-2 and IL-3 release occurred with the combined insult than after bony injury or tissue trauma alone with hemorrhage. The present study suggests that different traumatic insults, i.e. bone fracture as well as soft-tissue trauma in conjunction with hemorrhagic shock, produce comparable depression of host immune function. Moreover, combination of closed bone fracture and soft-tissue trauma prior to hemorrhagic shock leads to even more compromised immunity. This indicates that different mechanisms of immune depression may be involved following soft-tissue trauma or bony injury coupled with hemorrhage. The markedly depressed immune function following bony injury, soft-tissue trauma and hemorrhagic shock may contribute to the increased susceptibility of severely injured patients to sepsis and the ensuing multiple organ failure in the clinical situation.

Animals↗

PubMed1998

Laparoscopic splenectomy for idiopathic thrombocytopenic purpura. A 1-year follow-up study.

BACKGROUND: Laparoscopic splenectomy is a novel approach for the treatment of idiopathic thrombocytopenic purpura (ITP) in patients requiring surgical intervention. This technique was used for treatment in 16 consecutive patients. Follow-up was initiated at a median of 13.5 months after surgery to determine whether or not laparoscopic splenectomy is a safe and successful procedure that should be used in all patients requiring splenectomy for ITP. METHODS: Sixteen patients underwent laparoscopic splenectomy for ITP between May 1994 and September 1996. They were evaluated prospectively prior to surgery, immediately following surgery, at discharge, and at 13.5 months following surgery (n = 14) to determine the short- and long-term results of the procedure. RESULTS: Mean operation time was 123.4 +/- 12.1 min, and there were no significant intra- or postoperative complications. Mean intraoperative blood loss was 437.5 +/- 73.5 ml. Autologous blood transfusion was necessary in one patient (6.3%). Mean organ weight was 202.2 +/- 47.3 g. Mean postoperative hospital stay was 4.6 +/- 0. 4 days. Before discharge, mean platelet count rose by 100.7%. At follow-up (13.5 months postoperatively), it was 77.7% above preoperative values. No additional surgery was necessary in any of the patients undergoing laparoscopic splenectomy, and hematologic success was achieved in 12 patients (85.7%). CONCLUSIONS: Our results clearly indicate that laparoscopic splenectomy is a safe and successful procedure in patients suffering from ITP. It offers the well-known advantages of minimal invasive surgery as well as the surgical effectiveness of the open approach. This surgical technique should therefore be considered in all patients requiring splenectomy for the treatment of ITP.

Adolescent↗

PubMed1998

Severe depression of host immune functions following closed-bone fracture, soft-tissue trauma, and hemorrhagic shock.

OBJECTIVE: To determine the contribution of soft-tissue trauma plus hemorrhage, bone fracture and hemorrhage, as well as the contribution of bone fracture, soft-tissue trauma and hemorrhage on host immune function. SUBJECTS: Adult male mice (n = 6/group). DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory at a university-affiliated hospital. INTERVENTIONS: Closed-bone fracture (right lower leg; external fixation) and/or soft-tissue trauma (2.5-cm midline laparotomy, closed in two layers) were induced before hemorrhagic shock (mean arterial blood pressure of 35 +/- 5 (SEM) mm Hg for 90 mins, followed by fluid resuscitation) in male C3H/HeN mice and the animals were killed at 72 hrs after initiation of the experiment. MEASUREMENTS AND MAIN RESULTS: Splenocyte interleukin (IL)-2 and IL-3 release capacity, as well as splenic and peritoneal macrophage IL-1 and IL-6 release capacity were determined. Different traumatic insults, i.e., bone fracture or soft-tissue trauma in conjunction with hemorrhage, produced comparable immune depression. More significant depression of splenocyte IL-2 and IL-3 release capacity as well as macrophage IL-1 and IL-6 release capacity occurred with the combined insult (i.e., bone fracture/soft-tissue injury and hemorrhage) than after bone injury or tissue trauma alone with hemorrhage. CONCLUSIONS: The combination of closed-bone fracture and soft-tissue trauma before hemorrhage leads to even more compromised immunity than either soft-tissue trauma or closed-bone fracture along with hemorrhage. The markedly depressed immune function following bone injury, soft-tissue trauma, and hemorrhagic shock may contribute to the increased susceptibility of severely injured patients to sepsis and the ensuing multiple organ failure in the clinical situation.

Animals↗

PubMed1998

Metoclopramide: a novel and safe immunomodulating agent for restoring the depressed macrophage immune function after hemorrhage.

BACKGROUND AND OBJECTIVE: Recent studies have shown that administration of the anterior pituitary hormone, prolactin, after hemorrhage restored the depressed immune responses that are observed under those conditions. Because metoclopramide (MCP) is known to increase prolactin secretion and ultimately plasma prolactin levels, we attempted to determine whether administration of metoclopramide after hemorrhage produces any beneficial effects on the depressed splenocyte and peritoneal macrophage immune function after severe hemorrhage. DESIGN, MATERIALS AND METHODS: Mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 minutes, then adequately resuscitated and segregated into two groups. One group received saline vehicle; animals in the other group were treated with metoclopramide (100 microg/100 g body weight, subcutaneously) before resuscitation. Two hours after saline or MCP injection, the animals were killed and macrophage as well as splenocyte cultures established. Plasma corticosterone levels were also measured. RESULTS: The proliferative capacity of the splenocytes as well as their ability to release interleukin (IL)-2 and IL-3 in response to mitogen was markedly improved in animals that had hemorrhaged and that were treated with MCP compared with saline-injected mice. Moreover, the depressed splenic and peritoneal macrophage IL-1 and IL-6 release after hemorrhage was restored with MCP treatment. Furthermore, treatment with MCP prevented the increase in blood corticosterone levels seen after severe hemorrhage. CONCLUSION: These results support the concept that the immunosuppression after hemorrhage may be mediated by hormones from the hypothalamic-pituitary-adrenal axis. Furthermore, MCP may be a useful adjuvant in the treatment of the trauma-hemorrhagic shock-induced immunosuppression.

Animals↗

PubMed1998

[Laparoscopic splenectomy--surgical and hematological results in the first 35 consecutive patients].

UNLABELLED: Aim of the present study: Laparoscopy offers a novel surgical approach for splenectomy. This prospective study with 35 patients requiring splenectomy examines the surgical and hematologic as well as oncologic safety of this procedure. METHODS: In 35 patients (16 male, 19 female) hematologic, surgical and clinical data were obtained prospectively to evaluate the surgical and hematologic as well as oncologic safety of laparoscopic splenectomy. Long-term follow-up data are available for 23 patients at a median of 17 months postoperatively. RESULTS: Mean operation time was 130.0 +/- 8.5 minutes and despite of blood loss > or = 1000 ml (n = 5) no significant intraoperative complications were observed. Mean blood loss was 460.0 +/- 69.2 ml and blood transfusions were necessary in 3 cases (8.6%; 1 x autologous blood). Mean organ weight was 270.5 +/- 34.7 g. Mean hospital stay postoperatively was 4.3 +/- 0.3 days and 2 revisions were necessary (5.7%). A significant rise in platelet count from 114.8 +/- 14.6 G/l to 235.0 +/- 23.6 G/l was observed postoperatively which could be confirmed in long-term follow-up (213.4 +/- 32.0 G/l; p < 0.05). Thrombocytopenic patients also showed this significant rise in platelet count. The initially significant fall in hemoglobin from 13.5 +/- 0.4 g/dl to 10.9 +/- 0.3 g/dl returned to 14.0 +/- 0.4 g/dl at follow-up. Anemic patients showed a significant rise of hemoglobin at follow-up evaluation (p < 0.05). In this series of 35 consecutive patients to conversion was necessary, no mortality was observed, perioperative morbidity was 2.9% and hematologic success could be achieved in 20 (85.7%) patients available for follow-up evaluation. CONCLUSIONS: Laparoscopic splenectomy is a safe and successful surgical procedure in patients requiring splenectomy for benign hematologic diseases. This approach offers the advantages of minimal invasive surgery and should be considered in all patients requiring splenectomy.

Adult↗

PubMed1997

Trauma-hemorrhage induces increased thymic apoptosis while decreasing IL-3 release and increasing GM-CSF.

Although the thymus is an important organ in the ontogeny of T lymphocytes, little is known about the effects of hemorrhage and/or trauma on this organ. The objective of this study was to determine whether trauma-hemorrhage induces increased thymic apoptosis and, if so, which mediators may be involved. Male C3H/HeN mice underwent either sham operation, hemorrhagic shock (mean artery blood pressure of 35 +/- 5 mmHg for 90 min, followed by blood and fluid resuscitation), fracture of the right tibia, or fracture plus hemorrhage, respectively. At 3 days after the procedure, total viable thymocyte yield, thymocyte apoptosis (flow cytometry), thymus-derived IL-3 (bioassay), and GM-CSF (ELISA) were determined. The results demonstrate that fracture alone induces no significant change in the parameters measured. However, (i) there was a significant decrease in total viable thymocyte yield and an increase in thymocyte apoptosis following hemorrhage or fracture plus hemorrhage; (ii) thymocyte IL-3 release was significantly reduced after hemorrhage as well as fracture plus hemorrhage; (iii) thymus-derived GM-CSF was significantly increased after fracture plus hemorrhage, but not with hemorrhage alone. In conclusion, severe hemorrhage alone or coupled with fracture can induce thymus atrophy via apoptosis. In addition, the decreased IL-3 release suggests that apoptotic thymic involution may be due to the lack of growth factor support. Such dyshomeostasis may contribute to inappropriate/inadequate T cell maturation leading to host immune suppression following trauma-hemorrhage. Increased thymus-derived GM-CSF might be in part responsible for the systemic inflammatory response following trauma-hemorrhage.

Animals↗

PubMed1997

Testosterone receptor blockade after hemorrhage in males. Restoration of the depressed immune functions and improved survival following subsequent sepsis.

BACKGROUND: Recent studies suggest that androgen depletion by castration before hemorrhage has protective effects on cell-mediated immunity in male mice after soft tissue trauma and hemorrhagic shock. OBJECTIVE: To determine whether treatment with an androgen receptor blocker (eg, flutamide) after trauma-hemorrhage and sepsis has any salutary effects on cell-mediated immunity and on the survival of male animals under those conditions. DESIGN: Male C3H/HeN mice were either sham operated or subjected to hemorrhagic shock (mean [+/- SEM] blood pressure, 35 +/- 5 mm Hg for 90 minutes) followed by adequate fluid resuscitation (with shed blood and lactated Ringer solution). The animals then received either vehicle or 25-mg/kg body weight flutamide subcutaneously immediately after the resuscitation as well as 24 and 48 hours thereafter. At 48 hours after shock, sepsis was induced by cecal ligation and puncture. Sham-operated animals underwent laparotomy only. At 24 hours after cecal ligation and puncture, the animals were killed, blood was collected, and splenocytes and splenic macrophages were harvested to produce nonadherent and adherent cultures. Splenocytes were evaluated for splenocyte proliferation and interleukin 2 release, while interleukin 1 and interleukin 6 release were assayed in splenic macrophages. Plasma testosterone and corticosterone levels were also measured by radioimmunoassay. In a separate set of experiments, survival was measured over a period of 9 days after the induction of sepsis. RESULTS: Hemorrhage followed by sepsis produced a significant (P < .05) depression of splenocyte and macrophage functions in vehicle-treated animals. In contrast, animals treated with flutamide showed markedly improved immune functions, as evidenced by restoration of splenocyte proliferation, interleukin 2 release, splenic macrophage interleukin 1 release, and improvement of splenic macrophage interleukin 6 release. Plasma corticosterone levels were notably elevated while testosterone levels were depressed after hemorrhage and the induction of sepsis. The survival rate of the animals in the flutamide-treated group was also notably higher than the survival rate of animals in the vehicle-treated group subjected to hemorrhage and sepsis. CONCLUSION: The findings that flutamide not only markedly improves the depressed immune functions but also the survival of animals after hemorrhage and the induction of sepsis suggest that the short-term administration of androgen receptor blocker in males after trauma represents a safe and novel approach for preventing immune deficiency and decreasing the mortality rate from subsequent sepsis.

Androgen Antagonists↗

PubMed1997

Effects of prolactin and metoclopramide on macrophage cytokine gene expression in late sepsis.

Previous studies indicate a profound suppression of tumour necrosis factor alpha (TNF-gamma), IL-1 beta and IL-6 release capacity by peritoneal macrophage (PM phi), splenic macrophage (SM phi) and Kupffer cells (KC) during late sepsis. Such a loss of functional capacity may reduce the animal's ability to ward off infection. Prolactin is known to enhance monocyte, T- and B-lymphocyte immune responses under normal conditions and has beneficial effects on cell-mediated immunity after haemorrhage. In the respect, the dopamine antagonist, metoclopramide, has been reported to increase circulating prolactin levels. Nonetheless, it remains unknown whether prolactin or metoclopramide have any salutary effect on macrophage (M phi) cytokine gene expression following sepsis. To study this, male C3H/HeN mice were subjected to sepsis and immediately thereafter were treated with prolactin (100 micrograms/25 g body weight, s.c.), metoclopramide (100 micrograms/100 g BW, s.c.) or given saline. PM phi, SM phi and KC (only SM phi and KC in metoclopramide-treated animals) were isolated at 24 h after sepsis. The monolayers were stimulated with or without LPS 10 micrograms/ml for 1 h in vitro. Total RNA was extracted and mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). A significant depression of constitutive and inducible mRNA levels of IL-1 beta, IL-6 and TNF-alpha in all three M phi populations were observed, when compared with shams (with exception of KC IL-6 mRNA in unstimulated cells). Prolactin as well as metoclopramide treatment after the onset of sepsis caused significant elevation of constitutive and inducible cytokine gene expression in all macrophages examined. Thus, prolactin and metoclopramide enhance the depressed M phi gene expression and may be useful in improving cell-mediated immunity during sepsis.

Animals↗

PubMed1997

[Immunology in the severely injured].

Immunological complications frequently occur during the clinical course in patients with multiple injuries. The increased release of pro-inflammatory mediators during the immunological response to trauma may lead to the systemic inflammatory response syndrome (SIRS) and furthermore, to multisystem organ failure (MOF), which is associated with a mortality of up to 80%. The development of multiple organ failure following major trauma is associated with remote organ failure, the dysfunction of organs which were not initially affected by the trauma. This manuscript reviews recent data in experimental trauma research and offers a more detailed evaluation of the immunological findings in trauma patients. In particular, the role of pro- and anti-inflammatory cytokines in the development or SIRS, MOF and ROF is discussed. Despite the enormous progress in clinical immunology and the available data on trauma-induced immune dysfunction, a large number of questions still remain to be answered before the immunological alterations following severe trauma can be beneficially influenced by immunomodulatory therapeutic efforts.

Acute Disease↗

PubMed1997

Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males.

OBJECTIVES: To determine: a) whether the cell-mediated immune response during sepsis differs in females vs. males; and b) whether the survival rate in females is different than in males after a septic insult. DESIGN: A prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female proestrus C3H/HeN mice. INTERVENTIONS: After anesthesia, male and proestrus female mice underwent cecal ligation puncture to induce sepsis. The mice were killed at 24 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: Splenocyte proliferation, as well as splenocyte interleukin (IL)-2 and IL-3 release, was determined by bioassay. In additional studies, survival rate after septic challenge was measured over 10 days. Splenocyte proliferative capacity and splenocyte IL-2 and IL-3 release were markedly decreased in male, but not in female, septic mice. Furthermore, the survival rate of septic female proestrus mice was significantly higher than in comparable male mice. CONCLUSIONS: These results support the concept that the immune response of females differs from males, and that females are immunologically better positioned to meet the challenge of sepsis.

Adolescent↗