Biomedical subjects
D Berger
Publications and source records attributed to D Berger.
Perioperative endotoxemia and bacterial translocation during major abdominal surgery: evidence for the protective effect of endogenous prostacyclin?
OBJECTIVE: To investigate the potential role of endogenous prostacyclin (PGI2) released after mesenteric traction during major abdominal surgery on perioperative endotoxemia and bacterial translocation. DESIGN: Prospective, randomized, double-blind clinical study. SETTING: Operating room and surgical intensive care unit in a university hospital. PATIENTS: Fifty consecutive patients scheduled for major abdominal surgery (pancreas resection, abdominal aortic surgery). INTERVENTIONS: Fifteen minutes before skin incision, either 400 mg of ibuprofen or a placebo equivalent were administered intravenously. Immediately after peritoneal incision, eventration and action of the small bowel was intentionally performed in a uniform fashion. MEASUREMENTS AND MAIN RESULTS: Baseline values were obtained before induction of anesthesia. Additional measurements, along with assessments of hemodynamics and gas exchange, were performed before incision of the peritoneum and at 5, 30, and 45 mins and 3, 6, and 24 hrs after mesenteric traction. Arterial plasma concentrations of 6-keto-prostaglandin F1 alpha and thromboxane B2 (stable metabolites of PGI2 and thromboxane A2) were determined by radioimmunoassay. Endotoxin was measured by limulus amebocyte lysate test. Mesenteric lymph nodes were sampled in 31 patients (ibuprofen n = 14, placebo n = 17) and sent for culture under sterile conditions. Transient hypotension and a marked increase of plasma 6-keto-prostaglandin F1 alpha concentrations occurred up to 6 hrs after mesenteric traction in untreated patients with median peak concentrations (2243 vs. 72 ng/L [p < .0001, placebo vs. ibuprofen], observed 5 mins after mesenteric traction). Endotoxemia occurred in both study groups. However, after mesenteric traction, plasma endotoxin concentrations were significantly higher in the ibuprofen group. Median peak concentrations (0.12 vs. 0.27 EU/mL [p < .001, placebo vs. ibuprofen]) were observed 3 hrs after mesenteric traction. Gram-negative bacteria in mesenteric lymph nodes were detected exclusively in the ibuprofen group (n = 5, p < .01). CONCLUSIONS: In ibuprofen-pretreated patients, significantly higher endotoxin concentrations as well as bacterial translocation to mesenteric lymph nodes occurred, despite the absence of a transient decrease in mean arterial pressure that had been associated with PGI2 release. Therefore, we hypothesized that during major abdominal surgery, endogenous PGI2 released in response to mesenteric traction may play a crucial role in maintaining splanchnic microcirculation and thus preserving gut mucosal barrier function.
Evaluation of the first Medical Psychiatry Unit in Japan.
The first Medical Psychiatry Unit (MPU) in Japan was established in 1990. The clinical experience during the first 4 years of this unit is presented, and the characteristics of the Unit between its first 2 years and its latter 2 years are compared. The number of patients, the average length of stay, the primary psychiatric disorders, the combined physical diseases and their outcomes are presented. The data suggest that while the experience of the MPU is limited, it plays an important role in Japan as (i) an appropriate clinical setting for patients with combined medical and psychiatric illness, (ii) a strategic model for dealing with psychiatric patients in the general hospital, (iii) an educational setting for psychiatric residents to become more familiar with medicine and surgery, and (iv) an opportunity for non-psychiatric residents to become familiar with psychiatric illnesses and treatments.
Endotoxin-induced release of interleukin 6 and interleukin 1 beta in human blood is independent of tumor necrosis factor alpha.
It has been suggested that tumor necrosis factor alpha (TNF alpha) acts not only by direct toxicity, but also as a proximal mediator which is able to induce the production of other cytokines, especially interleukin 6 (IL-6) and interleukin 1 beta (IL-1 beta). In order to test the dependence of the release of these two cytokines from leukocytes upon induction by TNF alpha, we stimulated whole blood in vitro with TNF alpha and compared the cytokine levels with those induced by endotoxin. The cytokine release was also determined after stimulation by endotoxin with added TNF alpha and by endotoxin with monoclonal antibodies against TNF alpha (anti-TNF alpha) added in order to reduce TNF alpha. Unstimulated blood samples were used as controls. The plasma levels of both IL-6 and IL-1 beta were significantly higher after stimulation with endotoxin than after stimulation with TNF alpha. TNF alpha did not induce cytokine levels significantly higher than controls. The cytokine levels were the same whether or not anti-TNF alpha was included together with the endotoxin. Plasma from samples with added anti-TNF alpha had no detectable TNF alpha. Our results indicate that the leukocyte-derived production of IL-6 and IL-1 beta in whole blood is stimulated directly by endotoxin and is not mediated by TNF alpha.
Determination of endotoxin-neutralizing capacity of plasma in postsurgical patients.
In 92 patients who underwent abdominal and goiter surgery endotoxin and endotoxin-neutralizing capacity (ENC) were determined in plasma preoperatively and daily postoperatively. Endotoxin plasma levels started to increase on day 1 in patients who were laparotomized. Correspondingly ENC was reduced during the 1st postoperative week. Even on the 1st postoperative day determination of ENC made the differentiation between patients possible who showed an uneventful course and patients who developed pneumonia, pulmonary failure, or mental disorders. Furthermore the need for diuretics in order to maintain sufficient renal function was associated with lower ENC during days 1-3. Endotoxin plasma levels were significantly elevated in patients who developed pneumonia during days 1-4, whereas the occurrence of pulmonary failure was only correlated with elevated endotoxin levels on day 3. Endotoxemia was pronounced in patients needing diuretics on days 1, 4, and 5. In patients who underwent goiter surgery ENC changed significantly as found for endotoxin plasma values during the postoperative course. Determination of endotoxin and especially ENC with the use of the limulus amebocyte lysate test turned out to be a reliable method correlating with impending complications at least in postsurgical patients.
Comment on "Personality disorders and psychiatric symptoms in psoriasis": a critical analysis.
In 1995 Rubino, et al. reported that a cluster analysis provided evidence for four different personalities in patients with psoriasis. Because they did not include controls with other disfiguring chronic dermatologic conditions, did not relate severity of disfigurement or chronicity of the psoriasis with personality dysfunction, and did not assess pre- and post-onset of psoriasis personality structure, we do not think it is prudent at this time to draw conclusions about personality and psoriasis.
Plasma concentrations of endotoxin and antiendotoxin antibodies in patients with multiple injuries: a prospective clinical study.
OBJECTIVE: To investigate the time course of endotoxaemia and its effects on the synthesis of antiendotoxin antibodies in patients with multiple injuries. DESIGN: Prospective clinical study. SETTING: University hospital, Germany. PATIENTS: 40 Patients with multiple injuries and 20 healthy volunteers who served as controls. INTERVENTIONS: Blood samples were collected up to 10 days after injury and the concentrations of endotoxin, antiendotoxin antibodies to four endotoxins, and for anti-alpha-haemolysin of Staphylococcus aureus were measured. The kinetics of endotoxaemia and antiendotoxin antibodies were investigated. RESULTS: Endotoxaemia peaked 0-3 hours after injury at 0.425 EU/ml and decreased thereafter to 0.04 EU/ml within five days. Total concentrations of IgM, IgA, and IgG increased continuously after day 3 (p < 0.05), but the specific IgM response to all endotoxins was only temporary and the relative content of specific antibodies to all endotoxins peaked at day 3 (p < 0.05). Antiendotoxin antibodies of IgM class cross-reacted among themselves. There was no general increase in specific antiendotoxin antibodies of IgA and IgG class. The relative content of specific antibodies to alpha-haemolysin of S aureus of all classes of immunoglobulins (IgM, IgA, IgG) remained on the same level from day 0-10. CONCLUSION: Multiple injuries are associated with early and temporary endotoxaemia which causes specific increases in antiendotoxin antibodies of the IgM-class. IgM antibodies to endotoxins cross-react among themselves.
Molecular and immunohistochemical p53 status in liposarcoma and malignant fibrous histiocytoma: identification of seven new mutations for soft tissue sarcomas.
BACKGROUND: p53 mutations are the most frequently observed tumor-related genetic changes. Mutational analysis concerns mostly carcinomas and is not comprehensive for soft tissue sarcomas. Among soft tissue sarcomas, malignant fibrous histiocytoma (MFH) and liposarcoma represent the most frequent tumor types. Most of the few identified mutations for soft tissue sarcomas are localized in the core domain of p53. A correlation between p53 positive immunoreactivity, missense mutations, and a poor prognosis is generally assumed. However, the character of p53 mutations and their functional importance for the clinical process is still unknown. METHODS: Sixty-two soft tissue sarcoma samples were investigated for the presence of p53 mutations and for p53 immunoreactivity. Exons 4-9 of the p53 gene were amplified from genomic DNA with the polymerase chain reaction. A prescreen for mutations was performed by nonradioactive single strand conformation polymorphism analysis; striking cases were sequenced directly. For an evaluation of the immunohistochemical status, five p53 antibodies were used. RESULTS: In 10 tumor samples 7 new p53 mutations and one polymorphism were identified. Mutations were detected for five liposarcomas (four patients) and four MFHs (three patients). Of the seven mutations, three were missense point mutations, three were deletions, and one was a complex conversion. All mutations but one were localized in the core domain of p53. Of 62 tumor samples, 56% (14 of 32 liposarcomas and 21 of 30 MFHs) were positive for p53 immunostaining. CONCLUSIONS: The mutations identified in the core domain affect codons that are structurally or functionally involved in DNA binding. A relation between p53 positive immunoreactivity and a poor prognosis, but not with an exclusively high tumor grade, is evident. p53 mutations in soft tissue sarcomas have a similar spectrum to those in carcinomas.
New aspects concerning the regulation of the post-operative acute phase reaction during cardiac surgery.
During a cardio-pulmonary bypass, as well as post-operatively, high levels of endotoxin, interleukin-6 (Il-6) and C-reactive protein (CRP) were measured in 30 patients. A significant increase in endotoxin plasma level occurred during surgery, culminating in a peak during reperfusion. Plasma levels of endotoxin continued to be slightly raised until the fifth day after surgery, whereas those of Il-6 rose at the time the operation came to an end and were at their highest 6 h later. CRP levels were also high, post-operatively, and were markedly raised on day 2. A definite, statistically significant correlation between the plasma levels of endotoxin and Il-6 during the operation was established, leading us to conclude that the endotoxin liberated during cardiac surgery acts as the main trigger in the release of Il-6 and thus induces the post-operative acute phase reaction. There was no evidence of a correlation between CRP and endotoxin or Il-6 plasma levels.
Cognitive functioning in experimental hypoglycaemia assessed with event-related potentials.
Cognitive effects of experimentally induced hypoglycaemia were investigated by event-related brain potentials (ERPs) in auditory and visual classification tasks. In a cross-over design eight healthy male subjects (age 22-27 years) were studied under control conditions or following administration of 0.15 IU insulin kg-1. The ERPs showed preserved early cortical components, while the N2 component was greatly reduced in both modalities. P3 components did not show an influence of hypoglycemia. These results suggest that the cognitive deficits are due to an impairment of automatic feature extraction from the stimuli.
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Endotoxemia and mediator release during colonoscopy.
BACKGROUND AND STUDY AIMS: Previous clinical and experimental studies have shown evidence of a leakage of whole bacteria and bacterial products after major trauma through the gut barrier. By determining plasma endotoxin levels, products of the arachidonic pathway, interleukin-6, and the endotoxin-neutralizing capacity (ENC) of plasma during colonoscopy, we studied the gut barrier function and the pathogenetic sequelae of mediator release during a minimally invasive procedure. PATIENTS AND METHODS: Thirty-two patients were enrolled in a controlled prospective study. Endotoxin and ENC were determined by a chromogenic modification of the limulus amebocyte lysate test. Prostanoids and interleukin-6 were measured using commercially available ELISA tests. C-reactive protein levels were checked by nephelometry. RESULTS: Twenty-one of the 32 patients had elevated endotoxin plasma levels during colonoscopy. In one patient, gut-derived bacteria were detected in plasma. ENC decreased after 5 min, and thromboxane B2 levels also started to increase at that time. No acute-phase response took place after 24 h. CONCLUSION: During colonoscopy, endotoxin can be detected in blood. ENC measurement was shown to be even more sensitive. The pathogenetic sequelae leading to gut barrier failure remain unclear, because mediator release and endotoxemia, as checked by ENC, took place simultaneously.
Endotoxemia and specific antibody behavior against different endotoxins following multiple injuries.
The aim of this study was to establish the incidence of endotoxemia and the influence of endotoxin on specific antibody response after multiple injury. Blood samples were collected from 39 patients (median Injury Severity Score: 20.5) at 0-3 and 6-12 hours, and 1, 3, 5, and 10 days after admission. The endotoxin plasma levels were high at the first time point (mean = 0.421 endotoxin units/mL) and decreased in the later course. Total immunoglobulin levels of IgM, IgG, or IgA were low and increased throughout the observation period. Specific antibodies of the IgM class against two lipid A and four lipopolysaccharide preparations increased transiently but significantly on day 3 and/or day 5. No changes of specific antibody content against endotoxin or lipid A was seen in the IgG or IgA class. The specific antibody content of the different classes against alpha-hemolysin of Staphylococcus aureus did not differ during 10 days after trauma. The specific antibodies of the IgM class reacted with all lipid A and LPS lipopolysaccharide preparations demonstrating cross-reactivity. These results suggest that endotoxin may be a specific stimulator of IgM antiendotoxin antibody secretion following trauma.
Suicide risk in the general hospital.
This paper reviews the relationship between physical illness and suicide, reviews the studies of attempters and completers of suicide in general hospitals, and discusses those studies which have investigated the characteristics of patients in the medical setting with suicidal ideation. Study of suicidal ideation in a general hospital setting aimed at characterizing patients' suicidality may allow psychiatrists to better discriminate those patients at greater risk for completed suicide. Comparison of medical patients with suicidal ideation with those who had attempted or completed suicide, and recommendations to reduce suicidal impulses and treat these patients are discussed.
Incidence and pathophysiological relevance of postoperative endotoxemia.
Patients who underwent surgical procedures usually develop elevated body temperature, changes of plasma levels of some proteins, and leucocytosis. These alterations are summarized as the postoperative acute-phase reaction. Also endotoxin can induce the described phenomena suggesting that endotoxin may play a role concerning the induction of the acute phase reaction. In order to test that hypothesis we determined endotoxin plasma levels preoperatively and daily postoperatively in patients who were operated on because of goiter (n = 20), colonic, pancreatic and gastric diseases (n = 58). A significant increase of endotoxin plasma levels was found at the first and third day after abdominal surgery whereas after goiter surgery the increase revealed to be only very slight. However, the decrease between the first and second postoperative day in the latter group was again statistically significant suggesting postoperative endotoxemia even after minor operations. Furthermore a correlation between the amount of circulating endotoxin and pulmonary or infectious complications could be established in patients after major operations even at the first postoperative day suggesting a pathogenetic relevance of postoperative endotoxemia.
Relationship of parental bonding to child abuse and dissociation in eating disorders in Japan.
Parental bonding patterns were studied in 52 female Japanese eating disorder outpatients with and without histories of sexual or physical abuse and with dissociation. Instruments included the Parental Bonding Instrument (PBI), the Dissociative Experiences Scale (DES) and the Dissociative Disorders Interview Schedule (DDIS). Those with physical abuse history, but not sexual abuse history, had significantly different parental bonding scores and higher DES scores compared with subjects without physical abuse. DES scores and PBI scores were not correlated. Although the PBI was useful in discriminating between those with and those without abuse histories, it did not detect differences in degree of dissociation. Lack of association of sexual abuse to PBI and DES scores may have been due to mild abuse.
Use of a pedicled rectus abdominis muscle flap for repair of a failed vesicourethral anastomosis in a dog.
A 10-year-old mixed breed dog underwent a prostatectomy for an adenocarcinoma. Within three days the dog had signs of a uroperitoneum. Re-exploration revealed that a portion of the vesicourethral anastomosis had failed. Primary suturing of the tissue along the site of dehiscence following debridement of the devitalised tissue was impossible. A rectus abdominis muscle flap was created and successfully used to repair the site of leakage.
Sociocultural differences on hostility in alexithymic persons.
A recent comment by I. Alex Rubino on the personality correlates of alexithymia implied that there are several important areas for further discussion. Sociocultural differences in ethnicity (Japanese and Italian) may need to be taken into account for an understanding of the divergent findings.