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We aimed to assess the impact of the graft-recipient weight ratio (GRWR) on early post-transplant complications and patient survival rates in children after living donor liver transplantation (LDLT). We retrospectively analyzed 321 patients who underwent LDLT from 2004 to 2019. The recipients were categorized into four groups: 37 patients had a GRWR ≤ 1.5% (Group A), 196 patients had a GRWR &gt, 1.5% and ≤3.5% (Group B), 73 patients had a GRWR &gt, 3.5% and &lt, 5% (Group C) and 15 patients had a GRWR ≥ 5% (Group D). Incidence of early surgical complications including vascular complications, biliary complications, postoperative bleedings, gastrointestinal perforations and graft loss were comparable among groups with a different GRWR. Delayed abdominal wound closure was more common in patients with a GRWR &gt, 3.5%. Recipients with a GRWR &lt, 5% had a significantly better prognosis concerning patients and graft survival. Using grafts with a GRWR &lt, 5% allows us to expand the donor pool and decrease the risk of mortality while on the waiting list, when patients at the time of transplantation have less advanced liver disease. LDLT with a GRWR ≥ 5% is related to a higher risk of poor outcome, and thus should be an option for treating selected patients when the risk of a delayed transplantation is high and access to deceased donors is limited.

Graft versus host disease (GvHD) occurs in as little as 1–2% of cases after liver transplantation (LT), but is probably under-diagnosed and under-reported. Skin rash, diarrhoea, and/or fever are early symptoms of GvHD, and the most common causes of death are sepsis or gastrointestinal bleeding as a result of bone-marrow involvement. The delay in diagnosis as well as lack of standard treatment contributes to the high lethality of GvHD.

Iridium C,N-cyclometalated complexes with an ionic structure are considered to be promising candidates for application in host/guest solid-state phosphorescent single-layer devices because the employment of such dopants offers the possibility of reducing their concentration in organic matrices as well as allows obtaining organic light emitting devices (OLEDs) with interesting emission parameters. We report herein a methodology enabling the synthesis of cyclometalated ionic iridium(iii) complexes of the type [Ir(C^N)

Liver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects.was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw).Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures.Increased number of transplantations performed at the site was associated with increased age of the recipients (pLong-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.

Background. Computerized tomography-assisted volumetry permits one to estimate the volume of the liver graft as well as to monitor the regeneration in the donor for living-related liver transplantation (LRLT). Methods. The size of the whole liver and of the segments II, III, and IV was assessed in 64 living-related liver donors by preoperative computerized tomography (CT) volumetry. Segments II and III were harvested in 56 cases; segments II, III, and IV in 8 cases. The remnant liver was assessed by CT volumetry on postoperative days 7 and 30. Results. There was a linear correlation between the calculated volume of the graft and its weight (R = 0.61, P

Background CT-assisted volumetry permits an estimation of the volume of the graft in liver transplantation, as well as monitoring the donor's liver regeneration. The aim of the study was to observe the restitution of liver tissue in donors after harvesting of the liver fragment for living-related liver transplantation (LRLT). Methods The size of the whole liver and of segments II, III and IV was assessed by preoperative CT volumetry in 29 living-related liver donors. Segments II and III were harvested in 22 patients, segments II, III and IV in 6 patients. The remnant liver was assessed by CT volumetry on the 7th and 30th postoperative days. Results The correlation between the calculated volume of the graft and its weight was linear (r=0.56, p

The preliminary outcomes of patients with acute liver failure treated with the Prometheus Fractionated Plasma Separation and Absorption (FPSA) system are presented herein. Patients and methods The procedures were performed in 13 patients (4, intoxication by Amanita phalloides; 4, unknown reason; 3, acetaminophen intoxication; 1, Wilson disease, and 1, liver insufficiency after hemihepatectomy owing to metastases of colon adenocarcinoma). The patients were qualified for the procedure according to the King’s College Hospital criteria. The patients’ general status was assessed on basic of GCS, UNOS, and the 4-grade encephalopathy classifications. The procedures were performed with the Prometheus 4008H Fresenius Medical Care unit. Results The 29 procedures were of mean duration 6.5 hours. There were statistically significant reductions in total bilirubin, ammonia, and aminotransferase levels. In addition, the procedures corrected water, mineral, and carbohydrate disorders. One patient did not require liver transplantation. Seven patients received liver transplants: three patients with positive outcomes; two died due to septicemia within 30 days perioperatively, one died at 6 months after OLT owing to respiratory failure; and one, owing to hemorrhagic diathesis. Four patients did not receive a liver transplant because of lack of a organ, no consent for the surgery, or neoplastic disease with metastases. Conclusions The Prometheus FPSA-System was an effective detoxication method for patients with acute liver failure. The system was useful as a symptomatic treatment before liver transplantation allowing a longer wait for a graft.

The so-called learning factor has been disregarded for many years in analyzing the causes of surgical complications and post-operative mortality; it is also the case for OLT. In our center until April 2003, 209 OLT were performed in 196 patients. We evaluated the impact of experience of the transplantation team on the outcomes of liver transplantation. Thirty-four patients died (mortality rate, 16%) and 1-year survival rate, 64%. Mortality rates varied during different periods of observation due to increasing experience of the transplantation team. The causes of mortality were assessed for a series of 34 patients: it was 75% at the beginning of transplantation procedures while recent deaths have not recently exceeded 10% of cases.

The aim of the study was to estimate the risk of harvesting a liver fragment from a living-related adult donor. Liver fragments were harvested from 44 donors. Liver segments II and III were harvested from 36 donors. Liver segments II, III, IV were harvested from 6 donors, 2 donors gave segments V, VI, VII, and VIII. After preliminary donor selection volumetric assessment of liver segments by computed tomography and arteriography was performed to visualize the cenac trunk and superior mesenteric artery. None of the donors died. No complications were observed during the operation. Only one case, a bile collection, was observed after surgery. We treated this patient with a satisfactory result by sonography-guided drainage. We observed temporary elevation of bilirubin and transaminase levels and a decrease in prothrombin index value. Blood transfusion was not necessary during any of the procedures. Mean hospitalization time after the surgery was 9.4 days. Mean graft weight/recipient weight ratio was 2.54%. The risk of the harvesting liver fragment from a living-related adult donor seems to be minimal.

The aim of the study was to analyze indications and results of the first one thousand liver transplantations at Chair and Clinic of General, Transplantation and Liver Surgery, Medical University of Warsaw. Material and methods Data from 1000 transplantations (944 patients) performed at Chair and Clinic of General, Transplantation and Liver Surgery between 1994 and 2011 were analyzed retrospectively. These included 943 first transplantations and 55 retransplantations and 2 re-retransplantations. Frequency of particular indications for first transplantation and retransplantations was established. Perioperative mortality was defined as death within 30 days after the transplantation. Kaplan-Meier survival analysis was used to estimate 5-year patient and graft survival. Results The most common indications for first transplantation included: liver failure caused by hepatitis C infection (27.8%) and hepatitis B infection (18%) and alcoholic liver disease (17.7%). Early ( 6 months) retransplantations were dominated by hepatic artery thrombosis (54.3%) and recurrence of the underlying disease (45%). Perioperative mortality rate was 8.9% for first transplantations and 34.5% for retransplantations. Five-year patient and graft survival rate was 74.3% and 71%, respectively, after first transplantations and 54.7% and 52.9%, respectively, after retransplantations. Conclusions Development of liver transplantation program provided more than 1000 transplantations and excellent long-term results. Liver failure caused by hepatitis C and B infections remains the most common cause of liver transplantation and structure of other indications is consistent with European data.

Background. Living-related liver transplantation for pediatric patients has become an acceptable, low-risk treatment option. The aim of this study was to assess the extent of donor liver regeneration. Materials and Methods. Between October 1999 and January 2008, 120 living-related donors provided 109 grafts consisting of segments II and III and 11 grafts consisting of segments II, III, and IV. Volumetric assessment of the donor liver and selected segments was performed using computed tomography. After procurement every graft was weighed. At 7 and 30 days, as well as 12 months after the operation the donor liver remnant was evaluated for differences in volume. Results. A significant correlation was observed between the liver graft mass and its volume as assessed by computed tomography (r = 0.781; P < .05). Twelve months after procurement, the average regeneration index was significantly higher among donors of segments II, III, and IV (144 ± 23%) versus donors of segments II and III (114 ± 15%; P < .05). Conclusion. Liver regeneration after procurement of selected liver segments from living donors is a consistent finding. Computed tomography is an accurate imaging modality to track changes in liver volume. This study showed a positive correlation between the size of the liver graft and the regeneration of the liver remnant in the donor.

Biliary complications are known as a weak point of liver transplantation. Their occurence can be related to the practice of draining the biliary anastomosis performed at the time of transplantation. At our institution, routine of anastomotic biliary drainage was abandoned in June 2004. Aim We sought to assess the occurence and character of biliary complications following orthotopic liver transplantation in relation to the technique of anastomosis. Materials and Methods In two groups of transplantees: last 100 transplantations with biliary drainage (48 females and 52 males aged 17 to 64 years) and last 100 transplantations without drainage (52 females and 48 males aged 18 to 67 years). The results of treatment were compared, for biliary complications and their influence on further management. In both groups, the main indications for transplantation were various types of cirrhosis as well as cholestatic diseases. In most cases (167) we performed a cholangiojejunal Roux-en-Y (CBD) end-to-end anastomosis, less commonly (33 cases) hepaticojejunal anstomoses. Results In the first group, biliary complications (bile leak at the site of drainage, bile leak after T-tube removal, CBD strictures) requiring surgical or endoscopic intervention, occurred in 17% recipients. In one case, the biliary complication resulted in retransplantation. In the second group, biliary complications occured in 11% patients. None of them caused organ loss. Conclusion Abandoning drainage of the biliary anastomosis has reduced the occurrence of early biliary complications after orthotopic liver transplantation.

As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population—a good prognosis with improved nutritional status, respiratory function, and quality of life.

Introduction. Biliary complications are known as the weak point of liver transplantation. Their occurrence can be related to the practice of drainage of the biliary anastomosis, the routine use of which was abandoned in June 2004. The aim of the study was to assess the incidence and type of biliary complications following orthotopic liver transplantation in relation to the technique of biliary anastomosis. Material and methods. We compared the results of two groups of adult liver transplant recipients: group I, recent 50 transplantations with biliary drainage (25 women: 25 men of age range: 17 to 63 years), and group II, first 50 transplantations without drainage (19 women and 31 men of age range, 20 to 65 years). We examined the problem of biliary complications and their influence on the further management of the patients. In both groups the main indications for transplantation were various types of cirrhosis as well as cholestatic diseases. In the majority of cases (n = 86) an end-to-end common bile duct anastomosis was performed and in 14 cases, hepaticojejunal anastomosis. Results. In group I, biliary complications requiring surgical or endoscopic intervention occurred in 10 (20%) recipients. In one case, biliary complications resulted in the need for retransplantation. In group II, biliary complications occurred in only four (8%) patients, none of which caused organ loss. Conclusion. Cessation of biliary anastomosis drainage has reduced the occurrence of early biliary complications following orthotopic liver transplantation.

Introduction The number of available cadaveric donor organs has reached a plateau. One current solution has been to increase number of living related liver transplantations. Material and methods Since October 1999 in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 40 living related liver transplantation have been carried out. Results In 31 (77.5%) cases, a normal arterial supply was observed: the common hepatic artery arose from a celiac trunk. In two cases (5.0%), there was a partial arterial blood supply by the right accessory hepatic artery originating from the superior mesenteric artery. In two cases (5.0%), a right hepatic artery arose completely from the superior mesenteric artery (replaced artery). In one case (2.5%), a common hepatic artery originated from the superior mesenteric artery. In two cases (5.0%), an accessory left segmental artery originated from the left gastric artery. In two cases (5.0%), the function of an absent left hepatic artery was assumed by a replaced left hepatic artery originating from the left gastric artery. In two (5.0%) cases, there were two separate ducts draining the right hemiliver. There were two (5.0%) cases of an accessory duct draining segment IV, originating within the confluence of the right and left hepatic ducts. In one (2.5%) case, the common hepatic duct showed a trifurcation. Conclusion During harvesting from a living donor knowledge of anatomical variants must be used to optomize the liver graft.

Vascular complications following liver transplantation is reviewed based upon literature data and our own results. Our study conclusions are mostly based on literature data, because our center does not have the liver transplantation experience of other centers worldwide. Thus, we may conclude, that the number and character of complications does not differ from those reported by other centers. The enbloc technique used in liver harvesting minimizes the risk of arterial damage in case of vascular anomalies. Recipient retransplantation is the most effective treatment method in cases of hepatic arterial occlusion. Doppler ultrasound examinations are effective to monitor vascular blood flow in the transplanted liver.

BACKGROUND: Blood transfusions are associated with numerous clinical phenomena attributable to reduced posttransfusion immunocompetency. The exact mechanism by which blood transfusions induce a state of reduced immune responsiveness remains unclear. STUDY DESIGN AND METHODS: The effect of a large-volume blood transfusion on the frequency and responsiveness of immune cells in lymphoid compartments was examined in normovolemic rats. The effects of syngeneic and allogeneic blood transfusions were compared. RESULTS: The results in normovolemic rats were compared to those in nontransfused and saline-infused animals. In the normovolemic rats, there was a significant decrease in cells of erythroid lineage in bone marrow, with a slight increase in the percentage of cells in the bone marrow myeloid and lymphoid lineages; a significant increase in the percentage of the OX7+ Thy1+ cell population in bone marrow cells (stem cells are contained in this population) and blood cells; a decrease in the bone marrow OX6+ cell population (HLA class II-positive cells); a decrease in the responsiveness of blood, spleen, lymph node, and bone marrow cell populations to mitogens; and a downregulating effect of both syngeneic and allogeneic blood transfusions on hematopoiesis and cell responsiveness. CONCLUSION: Massive whole blood transfusion, either syngeneic or allogeneic, constitutes a strong downregulating signal for hematopoiesis, affecting the erythroid, myeloid, and lymphoid cell lineages. It leads also to an attenuation of the responsiveness of hematopoietic tissues to mitogenic stimuli.

This study is aimed at the clinical and morphological criteria of estimation of the liver harvested for transplantation. In the period from January 1996 to May 1997 our team obtained 26 livers at the multi-organ harvesting. Most of the donors were young people after the trauma of central nervous system. The liver was harvested according to the principles of Starzl's fast method with the successive preparation on the "cold table". The donor's clinical status was estimated, as well as appearance, density and colour of the organ, quality of perfusion with UW solution In 23 cases the histological examination of the harvested organ allowed to estimate the degree of steatosis, hepatocyte necrosis, vacuolar degeneration and other abnormalities. In 3 cases the graft was estimated only by means of macroscopic examination.As a result of clinical and histological findings 8 organs were considered as unsuitable for transplantation. In one case the histological findings were the contraindication despite the satisfactory macroscopic appearance of the organ 15 organs were successfully transplanted, proving the conformity of clinical and histological criteria. In 4 livers (15%) the abnormalities of arterial supply were found.Clinical and pathomorphological estimation of the harvested liver is adequate to it's suitability for transplantation, advisable for the centres initiating the liver transplantation program. Detailed analysis of the donor's clinical status and laboratory data and competent macroscopic estimation of the harvested liver allow the experienced surgeon to resign from the routine histological verification, which might be necessary in doubtful cases only.

The exact changes in cytokine production and clinical implications of the increased cytokine levels following operative trauma remain unclear. In this study, systemic production of a spectrum of cytokines, including IL1 alpha, IL1 beta, IL6, IL8, IL10, and IFN gamma, was examined in patients undergoing minor elective operative trauma. The levels of IL1 receptor antagonist (ra) and IL6 soluble receptor (sR) were also determined. Although there were no changes in IL1 alpha and IL1 beta plasma levels during the entire observation period, there was a significant rise in IL1 ra level in all patients between postoperative day 1 and postoperative day 14. A significant increase in the IL6 plasma level was seen on days 1, 3, and 7 after surgery and an increase in the IL6 sR level was observed on postoperative days 10 and 14. Interestingly, the IL8 plasma values had risen significantly on days 1 and 3 following the operation. In some patients, an elevation in IL10 plasma level was noted on days 1 and 3 postsurgery. Results demonstrated that even a minor surgical procedure such as cholecystectomy with uneventful wound healing was followed by an appearance in the blood circulation of significant levels of cytokines between day 1 and day 14 after surgery. These observations point to the necessity of searching for methods of down-regulating the systemic cytokine effects after surgical trauma for the routine postoperative management.

Blood transfusions (BT) should be considered as transplantation of blood elements. They evoke various alterations in the immune responsiveness of blood recipients, contributing to an increased risk of infection and cancer recurrence. The exact mechanism by which blood transfusions induce a state of reduced immune responsiveness remains unclear. Relatively little is also known about immune changes occurring in lymphoid compartments other than blood following blood transfusions. In the present study, the effect of syngeneic and allogeneic blood transfusions on hemopoiesis and immune responsiveness was examined in a rat model. Transfusions of both syngeneic and allogeneic blood caused an increase in the bone marrow myeloid and lymphoid lineage cell compartments as well as a rise in the percentage of OX7+ stem cells in bone marrow. It was followed by a release of OX7+ stem cells into blood circulation, higher in the case of rats transfused with syngeneic blood. The changes in hemopoiesis were accompanied by a diminished responsiveness of blood, spleen and bone marrow lymphocytes to mitogens in both groups of rats. Data point to early changes in distribution and reactivity of bone marrow and lymphoid cells following blood transfusion.

The authors present 225 patients with various forms of portal system venous thrombosis (PSVT), of various origin and etiology. The largest group (120 patients) were the young people suffering from portal hypertension due to pre-hepatic venous obstruction of uncertain etiology, lasting since childhood. The next group consisted of 75 patients with liver cirrhosis coexisting with PSVT. In other cases PSVT was diagnosed as coincident with: Budd-Chiari Syndrome (8 cases), liver tumors (9 cases), chronic pancreatitis (3 cases) and polycythaemia (2 cases). In 3 cases PSCT developed postoperatively and in 5 cases after oral contraceptives. Diagnosis of coexisting PSVT deteriorates the prognosis in liver cirrhosis. The overall mortality was 16%. The course of the disease depends on extensiveness and dynamism of thrombosis, but consequently leads to the development of portal hypertension. The most effective diagnostic procedures are: CT and USG with Doppler flowmetry. Bleeding esophageal varices require either sclerotherapy or surgical treatment--decompressive shunts or "non-shunt" procedures. In the cases of recent thrombosis, without bleeding varices, thrombolytic therapy appears to be effective.

Immune proteins and cytokine concentrations and activity were measured in skin tissue fluid-lymph and blood serum of patients with lower leg filarial lymphedema. High levels of lymph gamma-globulins, alpha-1-acid glycoprotein and IgG lymph/serum ratio were found. Lymph from filarial patients had an elevated lymph stimulatory effect on blood mononuclear cell culture with phytohemagglutinin. There was also a high concentration and activity of IL-1 beta but gamma-interferon was not detected. The deranged pattern of immune proteins and high activity of IL-1 suggest persistence of an ongoing local inflammatory process despite the absence of overt dermatitis. The high tissue-lymph IL-1 concentration and activity may signify a cytokine network promoting keratinocyte and fibroblast proliferation commonly seen on skin histology in patients with filariasis.

Cell-mediated immune responsiveness was evaluated in 8 patients with dilated cardiomyopathy (CDM). The percentage of blood OKM1 (monocytes), OKT3 (T-cells), OKT4 (helper cells), OKT8 (suppressor cells) and Leu7 (NK) positive cells remained within the normal range whereas the percentage of Leu11 (NK) and OKIa1 (Ia determinant) positive cells was found to be decreased. The natural killer (NK) cell cytotoxicity was significantly lowered. The ConA-suppressor cell activity was seen to be enhanced while the responsiveness of lymphocytes to ConA was diminished. Thus, no consistent numerical changes in lymphocyte subsets were observed in patients with CDM. Some functional deficiencies were, however, detected, and it is possible that these may play a role in the pathogenesis of CDM.

The influence of moderate operative trauma on lymphocyte responsiveness to phytohemagglutin (PHA) and in autologous mixed lymphocyte response (AMLR) was studied. Furthermore, production of interleukin 2 (IL2) and immunomodulatory effect of exogenous IL2 on lymphocyte reactivity after surgery were examined. The responsiveness to PHA declined on day 1 (p less than 0.05) and the level of AMLR was found decreased on days 1 (p less than 0.05), 3 (p less than 0.02) and 5 (p less than 0.03) after surgery. Production of IL2 significantly decreased on day 1, 3 and 5 (p less than 0.05) after operation. Supplementation of PHA and AMLR cultures with exogenous IL2 restored the attenuated postoperative responsiveness to the levels observed preoperatively. This observation may justify IL2 therapy in surgical patients with high risk of uncontrollable postoperative infections.

Lymph stasis in the extremities caused by interruption of lymphatics or insufficient lymph propulsion is often complicated by recurrent skin infections. To shed further light on this subject, we studied the phenotypical and functional characteristics of cells in peripheral lymph and skin of patients with obstructive lymphedema. Compared with controls, patients with secondary lymphedema displayed a high concentration of lymphocytes and erythrocytes in peripheral lymph, sometimes increased numbers of B cells, increased density of Langerhans cells in the epidermis and occasionally in the skin papillary layer, strong expression of class II antigens on skin endothelial cells and mononuclear infiltration around blood vessels, and margination of granulocytes in skin blood vessels. Reactivity of lymph cells to mitogens was augmented. Taken together these findings indicate that ongoing chronic inflammatory processes persist in skin with lymph stasis, and, moreover, with impaired lymphocyte and Langerhans cell trafficking from skin to regional lymph nodes and inefficient clearance of foreign antigens, these lymphedematous limbs become susceptible to infection.

The in vitro interleukin-1 (IL-1) and interleukin-2 (IL-2) production and IL-2 receptor (IL-2-R) expression by peripheral blood mononuclear (PBM) cells were examined in patients undergoing elective cholecystectomy. The IL-1 production by monocytes stimulated with a lipopolysaccharide (LPS) did not change on day +1 but increased by 57.5% on day +3 (p less than 0.05) after surgery, and was normalized on days +5 and +7. The IL-1 production by PBM cells stimulated by LPS increased by 97.6% on day +1 (p less than 0.05) and 109.5% on day +3 (p less than 0.05) after surgery, and became normalized on days +5 and +7. The IL-2 level in PBM cell supernatants stimulated with phytohemagglutinin (PHA) decreased by 45.2% on day +1 (p less than 0.05), 33.3% on day +3 (p less than 0.05), 32.3% on day +5 (p less than 0.05) and returned to the preoperative values on day +7. The IL-2-R expression on PHA-stimulated lymphocytes increased from 60.4 +/- 4.8% preoperatively to 67.2 +/- 1.9% on day +1 (p less than 0.05) but was again within the preoperative values on days +3, +5 and +7. In order to detect the described changes, stimulation with PHA had to be used. This indicates that simple surgical trauma produces subthreshold activation of blood immune cells. The cells enter the 'response alert' stage which can be measured after stimulation with lectins.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of 3 h lasting local hyperthermia on immune cell traffic through the normal human skin to afferent lymphatics, cell phenotypes, responsiveness, and stimulatory properties were studied in eight men. Cells were harvested from lymph drained from foot skin. Heating the skin in a water bath of 44 degrees C (skin temperature 2 mm under the surface 39 degrees C) evoked an augmented traffic of mononuclear cells to lymph with preponderance of large, macrophage-like, Ia-positive cells, among them Langerhans cells. Lymphocytes obtained from the heated skin lymph revealed in cultured increased spontaneous blastic transformation rate, augmented responsiveness to phytohemagglutinin (PHA), and enhanced PHA-presenting properties to autologous peripheral blood mononuclear (PBM) cells. An increased stimulatory activity on allogeneic mixed lymphocyte reaction (MLR) was also observed. Lymph from heated skin augmented the PBM responsiveness to PHA and showed increased interleukin-1-like activity. Local heating of the skin is a potent signal initiating augmented traffic, and enhanced responsiveness and stimulatory activity of "passenger" immune cells. Their rapid nonspecific activation makes them indiscriminately active against a wide range of antigens before the specific response is developed.

The effect of surgery on peripheral blood mononuclear cell responsiveness to mitogens and suppressor cell (SC) activity assessed in a concanavalin A (ConA) assay were studied in patients with stage 0 and stage III-IV cancer. Patients were exposed to a similar surgical trauma the same type of anaesthesia, and to no pre- and early postoperative radio- or chemotherapy. A more pronounced postoperative decrease in the lymphocyte count, responsiveness to phytohemagglutinin (PHA) and ConA, and in the SC activity was found in the nonadvanced than advanced cancer group. These findings point to an impaired mobilization and distribution capacity of circulating lymphocytes in patients with advanced neoplastic disease.

Lymphocytes in afferent lymph draining skin are derived from populations selected at the capillary level to enter the tissue space and which migrate spontaneously through the tissue to the initial lymphatics. These cells reveal a high spontaneous transformation rate in a 72 h culture. The mean 3H TdR incorporation was in a 24 h culture 2 times and in a 72 h culture 5 times higher than that of the peripheral blood mononuclear cells of the same subjects. The lymph cells responded significantly stronger to low concentrations of PHA, ConA and PWM than the blood cells. Also, the peak response of lymph cells was apparent at lower concentrations of mitogen in culture than of blood cells. The lymph cell population revealing a high spontaneous transformation rate was found to be the OKT4 enriched subset (induced/helper). The findings of a high spontaneous activation of lymphocytes which trafficked through the normal skin and defining this highly reactive subset as an OKT4-positive and strongly responsive to mitogens, reflect the in vivo immune events in the normal skin.

The influence of operative trauma on the quantity and proportion of cooperating mononuclear cells in peripheral blood of patients with stage 0 uterine cancer who underwent hysterectomy was studied using monoclonal antibodies. The percentage of OKM1+ cells (monocytes) had increased on day 1 by 12.4%, on day 3 by 24.8%, and had returned to normal by day 7. The percentage of large OKIa1+ cells (expressing la antigen) on day 1 was increased by 186.9%, while on day 3 it had returned to a normal level. There was a decrease on day 1 of the number and percentage of OKT3+ cells (all T lymphocytes) by 17.4%, OKT4+ cells (helper/inducer cells) by 27.9%, OKT8+ cells (suppressor/cytotoxic cells) by 24.6%, and small OKIa1+ cells by 49.4%. The number and percentage of T lymphocytes remained below the preoperative level throughout the observation period. However, the number of helper cells had increased significantly on day 5, while suppressor cells remained below the preoperative level during the entire observation period. The rising ratio of OKT4+/OKT8+ cells reflected the kinetics of recovery of the helper over the suppressor cell population.