Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production.

Interleukin 1 (IL-1) plays a central role in the regulation of the body's response to infectious and inflammatory stimuli. Recent evidence has shown that human platelets express a cell associated form of this proinflammatory cytokine very rapidly following activation. Since one of the earliest events in inflammation is frequently the rapid adhesion of platelets to injured endothelium, it was of interest to determine whether platelets express IL-1 in a functionally relevant form that can alter the phenotype of human endothelial cells in vitro. Thrombin activated platelets induced significant expression of the adhesion molecule intercellular adhesion molecule 1, as well as secretion of the IL-1 inducible cytokines IL-6 and granulocyte macrophage colony stimulating factor by cultured human umbilical cord and saphenous vein endothelial cells. This was inhibited by prior treatment of the platelets with antibody specific for IL-1. These results suggest that platelet delivered IL-1 might initiate and regulate some of the earliest phases of the inflammatory response. An additional observation of interest was differential induction of endothelial leucocyte adhesion molecule 1 by activated platelets on saphenous vein but not umbilical vein but not umbilical vein endothelial cells, which suggests functional heterogeneity of the endothelial cells.

Genitourinary trauma: a pictorial essay.

Genitourinary trauma is often overlooked in the setting of acute trauma. Usually other more life-threatening injuries take precedence for immediate management. When the patient is stabilized, radiologic imaging often plays a key role in diagnosing insults to the upper and lower genitourinary tract in the setting of trauma. Our aim is to provide a pictorial assay of imaging findings in upper and lower tract genitourinary trauma from a variety of mechanisms including blunt trauma, penetrating trauma, and iatrogenic trauma. A patient archiving and communication system will be used to review imaging studies of patients at our institution with genitourinary tract trauma. Cases of renal, ureteral, bladder, urethral, penile, and scrotal trauma will be considered for inclusion in our study. Multimodality imaging techniques will be reviewed. The imaging and pertinent findings that occur in various types of genitourinary trauma are outlined. Genitourinary trauma is often missed in the frenzy of acute trauma. It is important to have a high suspicion for injury especially in severe trauma, and in particular clinical settings. Although often not life threatening, recognizing the diagnostic imaging findings quickly is the realm of the astute radiologist so appropriate urologic management can be made.

Analysis of the platelet-type thrombin receptor in 20 cases of large granular lymphocyte proliferations.

The platelet-type thrombin receptor was expressed by large granular lymphocytes (LGLs) in a variety of proliferative diseases. Twenty patients with LGL proliferative disease were examined, including five T cell clones and a variety of polyclonal proliferations, some secondary to rheumatoid arthritis and Felty's syndrome; 17/20 showed high number of CD3+, CD8+, and CD57+ lymphocytes and 9/20 also had high numbers of CD16+ or CD 56+ positive lymphocytes. The thrombin receptor was present on more than 20% of the LGLs in 13/20 patients. The clonal T cell expansions showed the highest receptor expression with greater than 75% cells positive. Regression analysis of all 20 cases showed striking and highly statistically significant positive Spearman rank correlation between the proportion of thrombin receptor and CD57-positive LGLs (r = 0.56, P = 0.009). A negative correlation with CD56 was also found (r = -0.46, P= 0.043). Dual antibody flow cytometry showed the receptor was more often co-expressed with CD57 (64%) than with CD16 (19%) or CD56 (11%). The expression of the platelet-type thrombin receptor by LGLs of this phenotype raises the possibility of a functional role for thrombin in the pathogenesis of LGL proliferative diseases.

Antibodies against monocytes and endothelial cells in the sera of patients with atherosclerotic peripheral arterial disease.

We looked for antibodies against endothelial cells, monocytes, fibroblasts, lymphocytes and Epstein-Barr virus transformed lymphocytes in the sera of 28 elderly and 18 middle-aged patients with atherosclerotic peripheral arterial disease and 13 controls. Inclusion criteria were symptomatic peripheral arterial disease with intermittent claudication and ankle/radial Doppler pressure ratio less than 0.7 in the patient group and greater than 1 in the controls. The sera were tested using a standard cytotoxic technique against a cell panel of monocytes, T and B lymphocytes from 5 donors, and against endothelial cells, fibroblasts and Epstein-Barr virus transformed lymphocytes from one umbilical cord vein and blood. The sera of 30 of 46 (65.2%) patients showed toxicity against monocytes from at least one member of the cell panel and 12 of 19 sera tested (63%) reacted with endothelial cells. Only one of the control sera was positive against monocytes and none reacted with endothelial cells. None of the sera of either patients or controls contained cytotoxic antibodies against T and B lymphocytes, Epstein-Barr virus transformed lymphocytes or fibroblasts. The selective cytotoxicity suggests that the antibodies detected are not against HLA-antigens (which are expressed by normal lymphocytes and Epstein-Barr virus lymphocytes). Our results suggest that immune phenomena occur in atherosclerosis.

Interleukin 1 (IL-1) and tumour necrosis factor synergise in the induction of IL-1 synthesis by human vascular endothelial cells.

We have demonstrated that recombinant interleukin 1 (IL-1) induces IL-1 alpha and IL-1 beta production by human vascular endothelial cells (EC) in vitro. The effect of IL-1 on EC was dose-dependent and not due to contamination by endotoxin or secondary to the production of tumour necrosis factor (TNF). Thymocyte co-mitogenesis was shown to be due to IL-1 by treating EC supernatants with neutralising antibodies specific for IL-1 alpha and IL-1 beta. Recombinant TNF alpha synergised with IL-1 in the induction of IL-1 secretion by EC. Synergy was particularly striking at concentrations of IL-1 and TNF which, when used alone, had no effect - 2 U/ml IL-1 with 10 U/ml TNF. Thus we provide more evidence that EC play an important role in the perpetuation or possibly even initiation of chronic inflammation by amplifying cytokine production initiated by small numbers of infiltrating leucocytes.

Thymectomy for myasthenia gravis.

OBJECTIVES: To assess the change in clinical status of patients with generalized myasthenia gravis treated with thymectomy and to identify prognostic variables that may be of significance in optimizing patient selection. DESIGN: Retrospective review. Mean follow-up period was 41 months. SETTING: Large community hospital. PATIENTS: Thirty-seven patients (11 male and 26 female) with generalized myasthenia gravis who were referred for thymectomy if they were refractory to medical treatment or had a thymoma. This represents all patients undergoing thymectomy for myasthenia gravis between January 1982 and December 1991. INTERVENTIONS: Each patient underwent staging before and after thymectomy using a modified Osserman classification. Medication requirements were also recorded. All patients underwent transsternal thymectomy and complete mediastinal dissection. MAIN OUTCOME MEASURES: Changes in clinical stage and medication requirement before and after thymectomy; effect of patient age, sex, duration of disease, stage of disease, antibody status, histologic characteristics of the thymus, and duration of follow-up on outcome. RESULTS: Improvement after thymectomy was noted in all 37 patients. Complete remission was achieved in three patients (8%) and pharmacologic remission in 23 (62%). The remainder improved in stage, medication requirement, or both. Patients in preoperative stages IIb and IIc showed the greatest improvement. Age, sex, duration of disease, antibody status, histologic characteristics of the thymus, and duration of follow-up were not significant factors in assessing improvement. CONCLUSIONS: Transsternal thymectomy was found to be beneficial to all patients with generalized myasthenia gravis. Complete or pharmacologic remission was achieved in most patients (70%) following the procedure. Patients in preoperative stages IIb and IIc showed the greatest degree of postoperative improvement.

Nonoperative management of the adult ruptured spleen.

The risk of postsplenectomy sepsis has led to increased enthusiasm for preservation of the spleen. From January 1984 to December 1988, 51 consecutive adult patients with ruptured spleen sustained from blunt trauma were examined. Thirty-four patients (67%) had their conditions hemodynamically stabilized at the time of hospital admission and were placed on a regimen of strict bed rest with intensive monitoring. The average hemoglobin value at hospital admission in this group was 126 +/- 18 g/L, with an average drop of 17 +/- 14 g/L during their hospitalization; 14 patients required transfusions averaging 3 U each. Nonoperative treatment was successful in 33 (97%) of 34 patients; one patient whose condition deteriorated clinically underwent splenectomy on the fifth hospital day. These patients have been followed up for an average of 28 months with no sequelae from their splenic injury. We conclude that a nonoperative approach is a viable alternative in stable adult patients with splenic injuries due to blunt trauma when intensive monitoring is available.

Platelet activation by Protease I of Porphyromonas gingivalis W83.

Porphyromonas gingivalis produces a trypsin-like enzyme, Protease I, which is thought to be an important virulence determinant of the organism in adult periodontal disease. Protease I is transiently inhibited by physiological inhibitors of human thrombin. The aim of the present work was to establish whether Protease I was able to mimic thrombin by activation of the thrombin receptor on human platelets. Protease I caused true platelet activation at concentrations comparable to thrombin as measured by aggregometry, morphology and fluorescence flow cytometric analysis of CD63 expression. The effect was blocked by protease inhibitors but not by anti-thrombin receptor antibodies which, by contrast, blocked platelet activation by thrombin. We conclude that the activation of platelets by P. gingivalis Protease I involves proteolysis, but not scission of the thrombin cleavage site of the thrombin receptor.

A new method for the accurate localization of 239Pu in bone.

A new method for the localization of 239Pu in bone is described. The method, which is based on semi-automatic digitization of neutron induced autoradiographs, allows the 239Pu to be localized with respect to bone surfaces with an accuracy of +/- 2 micron. Results are presented for the distribution of 239Pu in the central lumbar vertebrae of female CBA mice at 24 h post-injection.

A semi-automated technique for assessing the microdistribution of 239 Pu deposited in bone.

A semi-automated analytical procedure is described for the localisation of 239 Pu in bone. The method is based on the use of a Quantimet 720B Image Analyser for the analysis of neutron-induced autoradiographs, and may be applied to most tissues with fissionable radionuclides. Compared with former methods the present technique offers improvements in accuracy and a considerable saving on time and manpower. These savings arise mainly from the ability of the Quantimet to be used for the automatic detection of the fission-fragment tracks and to operate directly on the neutron-induced autoradiograph without recourse to photography. Results are presented for the distribution of 239 Pu in the ilia of CBA mice at 24 h post-injection.

Heart valve ownership: legal, ethical and policy issues.

It is in the interest of parties to be able to test a defective explanted heart valve. This article identifies some of the relevant interests of patients (or their relatives), the manufacturers and society at large, and considers some of the legal issues involved in determining the ownership of valves in English law that arise from the varying nature of heart valves and the setting in which they are purchased and delivered. Ownership of explanted valves may vary according to whether the patient obtains the valve by private purchase, through the National Health Service, or through private health care insurance. It seems that, in the most common scenario (delivery via the National Health Service), the patient owns the valve (once implanted) by way of a gift, but that ownership revests to the health authority once the valve is explanted. The determination of ownership is, however, very complex. It is argued, however, that ownership does not automatically entail the right to test. So, even if it were determined that the patient (or the patient's estate) owned the valve, it would not follow that the patient had the right to control the testing of the valve or otherwise dispose of it. Close attention to the network of interests (both moral and socio-economic) in having explanted valves tested competently, suggests that it should be public policy to place custody of explanted valves (for the purposes of having them tested) in the hands of the Medical Devices Agency. This authority should be incorporated into regulation applying the European Community Medical Devices Directive.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic resection for metastatic colorectal carcinoma. William Beaumont Hospital experience.

Eleven hepatic resections have been performed at William Beaumont Hospital between April 1979 and April 1983 for metastatic colorectal carcinoma. Eight lesions were metachronous, and three were synchronous. All lesions except three metachronous lesions were solitary nodules. Patients who were found to have metachronous lesions were initially evaluated because of rising carcinoembryonic antigen (CEA) levels. One postoperative death occurred (9% mortality). All patients with synchronous lesions have since died for a mean survival of 15.2 months. The mean survival for patients with metachronous lesions, excluding the postoperative mortality, was 15.4 months (range, 4.1-30.7 months). The 1-year and 2-year actuarial survival rates are 79 per cent and 33 per cent. Five patients are alive, and three are free of clinical disease; therefore survival is expected to improve. In conclusion, rising CEA levels can be used to detect patients with metachronous lesions. The actuarial data support resectional therapy for metastatic colorectal carcinoma of the liver in carefully selected patients.

The sequential demonstration of non-specific esterase reactivity Ia antigen and Thy-1 antigen in murine epidermal sheets.

Immunofluorescence demonstrating Ia and Thy-1 antigens and non-specific esterase (NSE) enzyme histochemistry were performed sequentially on sheets of ear epidermis from CBA, C3H.OH, A/J, and Balb/c mice. The same areas of epidermis were photographed after each reaction and individual cells identified and compared. Thy-1+ dendritic cells expressed neither Ia antigen nor NSE reactivity. No cell was found to express Ia antigen or NSE alone: thus all Langerhans cells (LC) in normal murine epidermis appeared to co-express Ia antigen and NSE reactivity. LC expressing greatly increased amounts of Ia antigen were occasionally seen apposed to Thy-1+ cells suggesting that these cells may be immunologically active--perhaps involved in antigen presentation.

Hepatic resections: an eight year experience at a community hospital.

Between April 1979 and March 1987 24 patients underwent 26 hepatic resections. Colorectal liver metastases constituted the largest group (n = 18), followed by hepatocellular carcinoma (n = 2), Echinococcal liver cyst (n = 1), cholangiocarcinoma (n = 1), and leiomyosarcoma (n = 1). The mean age was 41.8 +/- 14.6 years (range: 23-69 years). Fifteen women and nine men comprised the group. The operative morbidity was 21 per cent, the 30-day operative mortality was 8 per cent (two deaths). Both operative deaths occurred in patients with colorectal liver metastases. The 18 patients with colorectal liver metastases included ten women and eight men. The mean age was 59.1 +/- 6.5 years (range: 46-69 years). There were seven synchronous and 11 metachronous liver metastases. Carcinoembryonic antigen (CEA) was found elevated in 14 of the original primary colonic carcinomas, and in all but one patient with metachronous liver metastases. The mean time from colorectal carcinoma resection to occurrence of metachronous metastases was 17.1 +/- 5.8 months. To date, 10 patients have had recurrences of liver metastases after hepatic resection for colorectal liver metastases. The mean time of recurrence was 12.6 +/- 11.9 months. The size of the metastases was 3.8 +/- 3.2 cm (range: 0.2-17 cm). The mean number of lesions present was 1.5 +/- 1.0. The 1 year and 2 year actuarial survival rates were 87.5 and 43.8 per cent respectively. The longest survivor is alive 54 months after his hepatic resection for colorectal liver metastases and remains to this date disease free.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonoperative management of adult blunt splenic trauma: a 15-year experience.

From January 1989 to December 1993, 40 consecutive adult patients with ruptured spleen from blunt trauma were examined. Fourteen patients (35%) were taken to the operating room initially because of hemodynamic instability and generalized peritoneal signs. Twenty-six patients (65%) were hemodynamically stabilized at admission and treated by nonoperative management, which included strict bed rest, intensive care unit monitoring, frequent physical examinations, and serial hematocrits. Four patients failed nonsurgical management and required a splenectomy, three because of clinical deterioration within 1 to 3 days of admission; the fourth patient had recurrent bleeding 7 days after injury. The patients in the operative group had a greater severity of injury with a mean injury severity score of 26.6, four deaths, and mean transfusion requirements of 3.7 to 4.0 units of blood, compared to a mean injury severity score of 14.6, one late death from cardiac causes, and average blood requirement of 0.4 to 0.7 units. Splenic injury grading averaged 3.2 in the surgical group (grade 1, one patient; grade 2, four patients; grade 3, eight patients; grade 4, no patients; and grade 5, one patient) and differed significantly from that of the nonoperative group (mean = 2.4; grade 1, 12 patients; grade 2, seven patients; grade 3, six patients; grade 4, two patients; and grade 5, no patients). Recent ultrasound analysis of select grades I to IV has shown excellent resolution or repair of these injuries. This report extends our series from 1978 to 1993 and includes 144 adult patients sustaining blunt splenic ruptures. Seventy-nine (55%) of these patients were treated nonsurgically. Seven patients (of 80) failed nonoperative management and required interval laparotomy, representing a 91 per cent success rate. Follow-up on more than 90 per cent of the patients has shown no sequelae from their splenic injuries. We conclude that adult patients with splenic injuries from blunt trauma who are hemodynamically stable and are without abdominal findings requiring celiotomy can be safely managed by a nonoperative approach.

A nonoperative approach to the adult ruptured spleen sustained from blunt trauma.

From 1978 to 1983, 53 consecutive adult patients with ruptured spleens documented by radionuclide studies, computerized axial tomography, or surgery, were evaluated at William Beaumont Hospital. Thirty-four patients (64%) underwent an exploratory laparotomy; 33 resulted in a splenectomy and one patient had an attempted splenorraphy which failed. Nineteen patients (36%) were hemodynamically stable on admission, or had transient episodes of hypotension readily reversed by intravenous fluids. They were placed at strict bedrest under intensive monitoring. Two patients deteriorated clinically and were taken to surgery, resulting in a splenectomy on the fourth and sixth hospital day, respectively. Seventeen patients (32%) were successfully treated nonoperatively, representing an 89 per cent success rate. The average admitting hemoglobin in the nonoperative group was 13.2 gm/dl, with an average drop of 1.6 gm/dl, and an average total blood transfusion of 1.2 units. These patients were followed for an average of 19.2 months, with no sequelae from their splenic injury. In a hemodynamically stable adult patient with a splenic injury sustained from blunt trauma, a nonoperative approach is a viable alternative when close intensive monitoring is available.

Hypothermia-induced coagulopathy during hemorrhagic shock.

A porcine model of hemorrhagic shock was used to study the effect of hypothermia on hemodynamic, metabolic, and coagulation parameters. The model was designed to simulate the events of severe blunt injury with hemorrhage occurring initially, to a systolic blood pressure of 30 mm Hg, followed by simultaneous hemorrhage and crystalloid volume replacement, followed by cessation of hemorrhage and blood replacement. Half of the animals were rendered hypothermic by external application of ice, and half remained normothermic. There was seven pigs in each group. Two deaths occurred in each during the hemorrhage phase. The hypothermic pigs demonstrated larger reduction in cardiac output than normothermic pigs. Volume replacement in the normothermic group restored cardiac output to baseline values. In the hypothermic group, cardiac output remained depressed despite volume replacement. Prothrombin times and partial thromboplastin times showed significantly more prolongation in the hypothermic group. Furthermore, this was not corrected by replacement of shed blood in the hypothermic group, as was seen in the normothermic group. We conclude that when shock and hypothermia occur together, their deleterious effect on hemodynamic and coagulation parameters are additive. The effects of hypothermia persist despite the arrest of hemorrhage and volume replacement. Thus, it is necessary to aggressively address both shock and hypothermia when they occur simultaneously.

Nonoperative management of blunt splenic injury in adults 55 years and older: a twenty-year experience.

The nonoperative management of splenic injury secondary to blunt trauma in older patients remains controversial. We have reviewed our experience from January 1978 to December 1997 with selective nonoperative management of blunt splenic injury in adults 55 years and older. Criteria for nonoperative management included hemodynamic stability with any transient hypotension corrected using less than 2,000 cm3 crystalloid infusion, a negative abdominal physical examination ruling out associated injuries, and a blood transfusion requirement of no more than 2 units attributable to the splenic injury. During the study period, 18 patients over age 55 with radiographic confirmation of a splenic injury met the above criteria for nonoperative management. Their mean age was 72 years (range 56-86), and 13 of the 18 were female (72%). The mean Injury Severity Score was 15 (range 4-29), with the mechanism of injury equally divided between automobile crashes (9) and falls (9). During a similar time period, 15 patients 55 years or older with splenic injury composed an operative group; these patients did not differ with respect to age (mean 68 years), sex (60% female), or mechanism of injury. CT scans of 8 patients managed nonoperatively were available and graded using the American Association for the Surgery of Trauma classification, with a mean score of 2.3 (range 2-3). Eight of the 18 nonsurgical patients received blood transfusions. None of the 18 patients who met the criteria for nonoperative management "failed" the protocol, and none were taken to the operating room for abdominal exploration. Two patients (11%) died of associated thoracic injuries after lengthy hospital stays, one at 10 days and one at 24 days. We conclude from our data that nonoperative management of blunt splenic injury in patients age 55 years and older is indicated provided they are hemodynamically stable, do not require significant blood transfusion, and have no other associated abdominal injuries.

Loch fleet: liming to restore a brown trout fishery.

This project has been successful in meeting its objectives in terms of demonstrating that catchment liming techniques can restore acidified waters to conditions suitable for fish populations for relatively long periods. This improvement in conditions has extended to the inlet stream, which provides vital fish spawning and nursery areas, which are difficult to treat effectively be other means in remote locations. The project has also provided an assessment of the effectiveness of differing rates and modes of lime application, which suggest that only quite restricted parts of a catchment require treatment. This not only maximizes the cost-effectiveness of the treatments, but also helps to minimize any side-effects on, for example, moorland vegetation. The biological monitoring programme at Loch Fleet has also provided an assessment of the overall ecological consequences of adding limestone to naturally acidic and calcium-deficient ecosystems.

Rapporteurs' report on discussions at the workshop on excess nitrogen deposition, Leatherhead, September 1987.

This paper reports major points from the discussions which took place during the Workshop on Excess Nitrogen Deposition.