Activation of TLR4 induces severe acute pancreatitis-associated spleen injury via ROS-disrupted mitophagy pathway.

Severe acute pancreatitis (SAP) is complicated by systemic inflammatory response syndrome and multiple organ dysfunction, the disease will eventually result in death in almost half of the case. The spleen, as the largest immune organ adjacent to the pancreas, is prone to damage in SAP, thereby aggravating the damage of other organs and increasing mortality. However, to date, the research on the mechanism and treatment of spleen injury caused by SAP is still in its infancy. Herein, we investigated the mechanism of spleen injury, and explored the application potential of tuftsin for relieving spleen damage in SAP mice. Firstly, SAP mice model was constructed via the retrograde infusion of 3.5 % sodium taurocholate into the biliopancreatic duct. Then, we proved that the up-regulation of Toll-like receptor 4 (TLR4) in spleen would lead to the accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction under SAP conditions. The splenic ROS and mitochondrial dysfunction could be improved by N-acetylcysteine (NAC) treatment or knocking out TLR4 in SAP mice. Meanwhile, we found that NAC treatment could also improve the autophagy of spleen tissue, suggesting that splenic ROS may affect impaired autophagy, causing the accumulation of damaged mitochondria, aggravating spleen damage. Furthermore, we verified the mechanism of spleen injury is caused by splenic ROS affecting PI3K/p-AKT/mTOR pathway-mediated autophagy. In addition, we detected the spleen injury caused by SAP could decrease the concentration of tuftsin in the serum of mice. Whereas, exogenous supplementation of tuftsin ameliorated the pathological damage, ROS accumulation, impaired autophagy, inflammation expression and apoptosis in damaged spleen. In summary, we verified the new mechanism of SAP-caused spleen damage that TLR4-induced ROS provoked mitophagy impairment and mitochondrial dysfunction in spleen via PI3K/p-AKT mTOR signaling, and the application potential of tuftsin in treating spleen injury, which might expand novel ideas and methods for the treatment of pancreatitis.

Ziziphus spina-christi leaf extract pretreatment inhibits liver and spleen injury in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects.

Sepsis is a systemic response to infection that can result in acute hepatic and splenic damage. Ziziphus spina-christi (L.) is a wild tree used as a medicinal plant by ancient Egyptians. However, little is known about the mechanism underlying its effects on sepsis. The current study investigated the protective effects of a Z. spina-christi leaf extract (ZSCLE) on liver and spleen damage in a male C57BL/6 mouse model of sepsis, induced by cecal ligation and puncture (CLP). Prior to CLP, ZSCLE was administered daily for five consecutive days via oral gavage at doses of 100, 200, or 300 mg/kg. The mice were euthanized 9 h after CLP, and oxidative stress markers were measured (myeloperoxidase, lipid peroxidation, nitric oxide, and reduced glutathione). In addition, we investigated histological changes, anti-oxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), cytokine levels, protein expression of nuclear factor-κB and inducible nitric oxide synthase (iNOS), and mRNA levels of mitogen-activated protein kinase (8, 9, and 14), iNOS, tumor necrosis factor-α, and interleukin-1ß. Our results indicated that ZSCLE significantly and dose-dependently inhibited sepsis-induced liver and spleen injury. These results suggest that ZSCLE could provide a therapeutic agent for sepsis by inducing anti-inflammatory and anti-oxidant effects.

Embolization for pediatric blunt splenic injury is an alternative to splenectomy when observation fails.

BACKGROUND: Management of splenic injury has shifted from operative to nonoperative management in both children and adults with reports of high success rates. Benefits of splenic conservation include decreased hospital stay, blood transfusion, and mortality, as well as avoidance of infectious complications. Angiography with embolization is an innovative adjunct to nonoperative management and has resulted in increased splenic salvage in adults; however, data in the pediatric population are scant. METHODS: A retrospective comparative study of a single-hospital trauma registry reviewed from 1999 to 2009. Patients 18 years and younger admitted with injury to the spleen were included. Children with penetrating injury were excluded. Children were divided into three categories by initial treatment: observation, embolization, or splenectomy. Data recorded include age, radiographic grade of injury, and Injury Severity Score (ISS). Groups were analyzed for success of initial treatment, requirement for transfusion of packed red blood cells, splenic salvage, and mortality. RESULTS: Registry review identified 259 children with blunt splenic injury. Initial treatment was observation in 227, embolization in 15, and splenectomy in 17. In the observation group, 9 (4%) of 227 children failed initial treatment; 8 of these underwent embolization, while 1 unerwent splenectomy. In the embolization group, 1 (7%) of 15 failed initial treatment and underwent splenectomy. Blood transfusion was required by 38 (17%) of 227 in the observation group, 6 (40%) of 15 (p = 0.02) in the embolization group, and 15 (88%) of 17 (p < 0.01) in the splenectomy group. Overall splenic salvage rate was 237 (92%) of 259. Three children died in the observation group, and four children died in the splenectomy group. There was no death in the embolization group. CONCLUSION: Splenic artery embolization for blunt trauma in children is associated with a higher blood transfusion rate compared with observation but offers a safe, intermediate alternative to splenectomy when observation fails. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Prothrombin complex concentrate versus recombinant factor VIIa for reversal of hemodilutional coagulopathy in a porcine trauma model.

BACKGROUND: Fluid resuscitation after traumatic injury may necessitate coagulation factor replacement to prevent bleeding complications of dilutional coagulopathy. Recombinant activated factor VII (rFVIIa) is being widely investigated as a hemostatic agent in trauma. Multicomponent therapy with prothrombin complex concentrate (PCC) containing coagulation factors II, VII, IX, and X might offer potential advantages. METHODS: Anesthetized mildly hypothermic normotensive pigs were hemodiluted by substituting 65% to 70% of total blood volume in phases with hydroxyethyl starch and red cells. Thereafter, animals received 12.5 mL . kg isotonic saline placebo, 35 IU . kg PCC, or 180 microg x kg rFVIIa. Immediately afterward, a standardized spleen injury was inflicted, and prothrombin time (PT) and hemostasis were assessed. Thrombin generation was also determined. RESULTS: Hemodilution depleted levels of factors II, VII, IX, and X markedly, prolonged PT and decreased thrombin formation. PCC and rFVIIa both fully normalized the hemodilution-induced lengthening of PT. In PCC recipients, peak thrombin generation was greater by a median of 60.7 nM (confidence interval 56.4-64.9 nM) compared with the rFVIIa group (p = 0.008). After spleen trauma, time to hemostasis was shortened to a median of 35 minutes in animals treated with PCC versus 94 minutes with rFVIIa (p = 0.016). CONCLUSIONS: In a pilot study involving an in vivo large-animal model of spleen trauma, PCC accelerated hemostasis and augmented thrombin generation compared with rFVIIa. Further investigations are warranted on PCC as a hemostatic agent in trauma.

Hemostatic efficacy of Ankaferd Blood Stopper in a swine bleeding model.

OBJECTIVE: The purpose of this study was to show the hemostatic effect of spray, solution and tampon forms of Ankaferd Blood Stopper (ABS), a unique medicinal plant extract historically used as a hemostatic agent in Turkish folklore medicine, in a porcine bleeding model. MATERIALS AND METHODS: Two 1-year-old pigs were used as bleeding models for superficial and deep skin lacerations, grade II liver and spleen injuries, grade II saphenous vein injury and grade IV saphenous artery injury. Spray, solution or tampon forms of ABS were applied after continuing bleeding was confirmed. The primary outcome was time to hemostasis. Volume of blood loss was not measured. The pigs were euthanized at the end of the experiment. RESULTS: Spray or direct application of ABS solution resulted in instant control of bleeding in superficial and deep skin lacerations as well as puncture wounds of the liver. A 40-second application of ABS tampon was sufficient to stop bleeding of skin lacerations, while 1.5- and 3.5-min applications were used to control hemorrhage from the saphenous vein and artery, respectively. No rebleeding was observed once hemostasis was achieved. However, repeated applications of ABS solution and tampon were only temporarily effective in the hemostasis of spleen injury. CONCLUSIONS: The data showed that ABS was an effective hemostatic agent for superficial and deep skin lacerations and minor/moderate trauma injuries in a porcine bleeding model.

[Blood reinfusion as an indicator of time-limit in the development of splenic injuries].

Literature data are analysed on the causes of differencies often encountered in practice between the time of injury by histological examination and time established in the course of legal investigation. An indirect marker--blood reinfusion--can limit the time of splenic damage creation.

Thermal injury resulting from application of a granular mineral hemostatic agent.

BACKGROUND: Uncontrolled hemorrhage accounts for the majority of deaths in combat. Effective topical hemostatic agents suitable for use on the battlefield may be valuable in controlling hemorrhage until definitive surgical intervention is possible. In an effort to identify a hemostatic agent suitable for battlefield use, we evaluated several potential hemostatic agents in a swine injury model and noted thermal injury to tissues with a granular mineral hemostatic agent (QuikClot). METHODS: Anesthetized swine were maintained with a mean arterial pressure in excess of 60 mm Hg. Cutaneous, muscular, hepatic, splenic, venous, and arterial wounds were created in a standardized fashion. Topical hemostatic agents were immediately applied to the wounds and the amount of bleeding and time to hemostasis were noted. RESULTS: The results reported here are part of a larger study in which a variety of hemostatic agents were evaluated. Only the findings related to the granular mineral hemostatic agent are discussed here. Application of the agent resulted in elevated tissue surface temperatures in excess of 95 degrees C and internal tissue temperatures exceeding 50 degrees C, 3 mm deep to the bleeding surface. Necrosis of fat and muscle were noted as well as full and partial thickness cutaneous burns. CONCLUSIONS: Topical administration of a granular mineral hemostatic agent to a variety of wounds in an experimental swine model resulted in thermal tissue injury and necrosis. Suggestions for reducing the extent of injury with this product are offered.

Comparison of poly-N-acetyl glucosamine with commercially available topical hemostats for achieving hemostasis in coagulopathic models of splenic hemorrhage.

BACKGROUND: The hemostatic quality of the poly-N-acetyl glucosamine (p-GlcNAc) patch was compared with a fibrin sealant, fibrin bandage, and cellulose patch. METHODS: A 2 x 2-cm capsular strip to a depth of 3 mm of the swine spleen was used as a source of bleeding. Splenic lacerations were created in hemophilia B dogs and treated with p-GlcNAc and Surgicel. Wounds were created in rabbits and treated with p-GlcNAc at 37degreesC and after keeping body core temperature at 29degreesC. RESULTS: Poly-N-acetyl glucosamine was able to achieve hemostasis with greater efficacy than either of the fibrin-based bandages. In the hemophilia B dog study, p-GlcNAc significantly outperformed Surgicel, with p-GlcNAc achieving hemostasis in 75% of the treated wounds compared with 17% for the cellulose patch. The hypothermia study demonstrated that p-GlcNAc is equally effective at 29degreesC and at 37degreesC. CONCLUSION: Poly-N-acetyl glucosamine was effective at controlling bleeding in animals with experimentally induced or genetic coagulopathic disorders.

Alternativas quirúrgicas a la esplenectomía postraumática, procedimientos de rescate esplénico en población pediátrica / Alternative procedures to splenectomy in pediatric population

Antecedentes: Hace cuatro décadas las normas del Departamento de Cirugía de nuestro Hospital, establecían esplenectomizar a los niños con bazos dañados, destacando que estas disposiciones eran reglas quirúrgicas con consenso mundial. Las graves complicaciones infecciosas, condujeron a desarrollar estrategias que permitieron realizar tratamientos quirúrgicos conservadores aun ante graves traumatismos. Objetivo: Conocer una serie de procedimientos alternativos a la esplenectomía, ya que la misma en pediatría conlleva un elevado riesgo de morbi-mortalidad por sepsis, sobre todo en menores de 5 años. Lugar de aplicación: Hospital de Niños Ricardo Gutierrez (HNRG) de Buenos Aires, Argentina. Diseño: Trabajo retrospectivo, observacional, no comparativo y cerrado. Población: Se trata de un grupo de 6 niños con lesiones esplénicas graves. Método: Fueron tratados mediante un protocolo normatizando en base a los criterios de atención inicial del curso ATLS del Colegio Americano de Cirujanos y el Comité de Trauma del HNRG. Para valorar el grado de lesión esplénica se utilizó el Organ Injury Scale OIS-(Spleen Injury Scale) y se categorizó la severidad de las lesiones utilizando el Abreviated Injury Scale 90. Resultados: Las cirugías realizadas (procedimientos operatorios alternativos a la esplenectomía), fueron las siguientes: 3 encestes con Vicryl Mesh, 2 ligaduras arteriales y 1 envoltura esplénica con parche de epiplón y bañado con adhesivo tisular. Todos los pacientes evolucionaron favorablemente. Conclusiones: En pediatría los traumatismos cerrados a nivel abdominal, en raras ocasiones requieren laparotomía, pero cuando esto sucede es recomendable que el cirujano maneje un amplio repertorio de técnicas quirúrgicas conservadoras y trabaje empeñado en no resecar el bazo, especialmente en niños menores de 5 años (AU)

Coagulation and temperature distribution in Nd: YAG interstitial laser thermotherapy: an in vitro animal study.

Interstitial laser thermotherapy (ILTT) was performed increasingly for local destruction of different tumours. The proposal of the present study was the optimisation of the therapy-relevant ILTT parameters and laser application forms which are a prerequisite for the development of an optimal tumour treatment strategy. Laser-induced temperature changes and coagulation patterns with different laser light applicators (bare fibre, ring mode fibre, side fibre, diffuser fibre) were investigated on liver, spleen and tongue tissues of 26 adult pigs after interstitial thermotherapy with Nd: YAG laser. Analysis of experimental results on ILTT and tissue necrosis showed a dependence on laser exposure time, type of laser fibre and applied laser energy. The most homogeneous and extensive coagulation zone was seen after laser treatment with rather low energy over a longer time period.

Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract.

To understand the bioavailability and mechanistic pathways of cytoprotection by IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) a series of in vitro and in vivo studies were conducted. Comparative protective abilities of GSPE, and vitamins C and E, singly and in combination, were assessed against smokeless tobacco extract (STE)-induced oxidative stress, DNA fragmentation and apoptotic cell death in a primary culture of normal human oral keratinocytes. GSPE protected against STE-induced oxidative stress, DNA damage and apoptotic cell death, and provided better protection as compared to vitamins C and E, singly and in combination. The bioavailability and protective ability of GSPE were examined against acetaminophen (AP)-induced hepato- and nephrotoxicity, amiodarone (AM)-induced lung toxicity, doxorubicin (DX)-induced cardiotoxicity and dimethylnitrosamine (DM)-induced spleenotoxicity in mice. GSPE-fed animals were compared with GSPE-untreated mice to evaluate the protective ability of GSPE against these structurally diverse drugs/chemicals. Serum chemistry changes, histopathology and DNA damage were evaluated. Results indicate that GSPE preexposure prior to the drugs/chemicals such as AP, AM, DX or DM treatment, provided near complete protection in terms of serum chemistry changes and inhibition of both forms of cell death, e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced in GSPE-fed animals. Histopathological examination of multiple target organs provided similar data. The results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against structurally diverse drug- and chemical-induced toxic assaults. Further, these studies exhibited a series of mechanistic information including free radical scavenging ability, anti-endonucleolytic activity, cytochrome P450 2E1 inhibitory activity, anti-necrotic, anti-apoptotic and anti-carcinogenic activities, modulatory effects on antioxidative and apoptotic regulatory genes such as Bcl2, c-myc and p53, which may be responsible for the novel chemoprotective properties exhibited by GSPE.

Protection against drug- and chemical-induced multiorgan toxicity by a novel IH636 grape seed proanthocyanidin extract.

Grape seed proanthocyanidins have been demonstrated to exhibit a broad spectrum of pharmacological, therapeutic and chemoprotective properties. In our previous studies, IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) demonstrated excellent concentration- and dose-dependent free radical scavenging abilities in both in vitro and in vivo models and provided significantly better protection than vitamins C, E and beta-carotene. GSPE demonstrated significant cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells and macrophage J774A.1 cells. In this study, the bioavailability and protective ability of GSPE were examined against acetaminophen-induced hepatoxicity, amiodarone-induced pulmonary toxicity, doxorubicin-induced cardiotoxicity, cadmium chloride-induced nephrotoxicity, dimethylnitrosamine-induced spleenotoxicity and O-ethyl-S,S-dipropyl phosphorodithioate (MOCAP)-induced neurotoxicity in mice. In each experiment, half of the test animals were orally fed GSPE for 7-10 days prior to drug/chemical exposure, while the other half received no GSPE. Parameters of analysis included changes in serum chemistry [alanine amino-transferase (ALT), blood urea nitrogen and creatine kinase], histopathology and integrity of genomic DNA. The results indicated that GSPE preexposure prior to the drugs/chemicals such as acetaminophen, amiodarone, doxorubicin, cadmium chloride or dimethylnitrosamine treatment, provided near complete protection in terms of serum chemistry changes (ALT, blood urea nitrogen and creatine kinase) and inhibition of both forms of cell death, e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced. Histopathological examination of the organs evaluated reflected similar patterns to those of the serum chemistry and DNA results. MOCAP exposure showed symptoms of severe neurotoxicity coupled with serum chemistry changes in the absence of any significant genomic change or brain pathology. GSPE afforded only partial protection in the brain tissue. These results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against drug- and chemical-induced toxic assaults.

[The use of laparoscopy in the diagnosis of a traumatic lesion of the spleen]. / Primenenie laparoskopii v diagnostike tramaticheskogo povrezhdeniia selezenki.

The results of laparoscopic diagnosis of splenic rupture in the closed abdominal trauma in 80 injured persons were analyzed. A splenic damage was excluded in 38 patients. In 12 of them hematoma, serohemorrhagic exudate, intestinal paresis were revealed. One patient with duodenal rupture was operated on, and in one more patient the idle laparotomy was conducted. Five patients died. According to the laparoscopic data a splenic rupture was diagnosed in 35 injured persons. Diagnostic failure was conceded in one patient, in whom a hepatic rupture was revealed while the laparoscopy conduction. A successful conservative treatment was conducted in three patients for subcapsular splenic hematoma. Relaparotomy conduction was needed in 3 patients. Three patients died: two of them--due to severe polytrauma and one--due to bronchopneumonia. One else patient died, which was hospitalized with severe polytrauma. In one patient bronchospasm have occurred.

Laparoscopic examination of the traumatized spleen with blood salvage for autotransfusion.

The management of splenic trauma presents a dilemma to the surgeon, who must weigh the risks of operative versus nonoperative management. Laparoscopy has been used increasingly for trauma cases to decrease the morbidity associated with standard laparotomy. Autotransfusion of the patient's shed blood has also become widespread to decrease the risks associated with transfusion. We describe the case of a 15-year-old male with blunt splenic trauma, in which laparoscopy was used to examine the spleen to ascertain the need for operative treatment, to look for other intra-abdominal injuries, and to salvage intraperitoneal blood for autotransfusion. In this case, laparoscopy determined that laparotomy would be nontherapeutic, and that autotransfusion could obviate the need for banked-blood transfusion.

Evaluation of a new hemostatic agent in experimental splenic laceration.

OBJECTIVES: To compare the effectiveness of several hemostatic agents and to evaluate a new hemostatic agent (ReClot) in controlling splenic hemorrhage. DESIGN: Rabbits were anesthetized and catheters placed. A celiotomy was performed and a splenic injury produced; hemostatic agent and compression were applied. EXPERIMENTAL GROUPS: In group 1 (n = 8), the splenic laceration was compressed with a dry sponge and 75 g of pressure until hemorrhage ceased. In groups 2, 3, and 4 (n = 10 each), splenic injury was treated with Avitene, Collastat, and ReClot, respectively. Hemostatic agent was applied to the splenic laceration and a dry sponge and pressure were applied as described for group 1. In group 5 (n = 9), a splenic laceration was produced, ReClot applied, and aggressive fluid resuscitation was initiated; the volume of crystalloid was adjusted to maintain mean arterial pressure. RESULTS: Application of a hemostatic agent reduced total blood loss compared with that measured in the control group, but there was no difference in blood loss among experimental groups treated with a hemostatic agent. The time required to achieve control of blood loss was less in the ReClot-treated group compared with the Avitene- and Collastat-treated groups. CONCLUSIONS: The hemostatic agent ReClot had a significant advantage over other hemostatic agents for the time required to achieve control of splenic bleeding. Aggressive fluid resuscitation did not limit the ability of ReClot to produce hemostasis.

[The arrest of hemorrhage in mechanical injuries to parenchymatous organs]. / Ob ostanovke krovotecheniia pri mekhanicheskikh povrezhdeniiakh parenkhimatoznykh organov.

The work describes results of the application of a new highly effective hemostatic drug--Caprofer. The investigations were performed in 61 rabbits who were given graded injuries of the liver, kidney and spleen. In all the cases hemostasis made its appearance quickly within 1-20 sec. after the application of Caprofer. Reliability of hemostasis was checked by the method of hydropressure of the organs under study which was shown to be very high. Caprofer was used under clinical conditions in 61 patients in operations for traumas and diseases of the liver, kidney, spleen, gallbladder and in resection of the prostate. The results obtained speak of high efficiency of Caprofer for parenchymatous bleedings. Pronounced adhesive properties of the drug were noted as well as the absence of undesirable side effects.

Laparoscopically guided blood salvage and autotransfusion in splenic trauma: a case report.

Salvage of intraperitoneal blood with autotransfusion is a well-accepted practice. Laparoscopic examination is gaining popularity and holds diagnostic promise for the evaluation of trauma patients. We describe herein the successful combination of these techniques in a patient who sustained blunt abdominal trauma, facilitating splenic salvage, autotransfusion, and avoidance of laparotomy.

[Heterotopic splenic autotransplantation: a therapeutic option in splenic trauma]. / L'autotrapianto eterotopico di milza: un'alternativa terapeutica nel trauma splenico.

The Authors report two cases of splenectomy for trauma, followed by heterotopic autotransplantation of splenic tissue in omental pockets. A follow-up nuclear scan and ultrasonography showed function and growth of the splenic implants. The pertinent surgical literature is reviewed.

Updating the management of salvageable splenic injury.

Because of the ready availability of autotransfusers and risk of transfusion-transmitted disease, the authors reexamined the management of splenic trauma. During the past 6 months, 20 adult and pediatric patients were treated for blunt splenic trauma. Nine had "minor" lacerations and were successfully managed nonoperatively. Eleven had ongoing hemorrhage or associated visceral injury necessitating laparotomy. In two, coexistent injuries were life threatening and total splenectomy was performed. The other nine had major splenic trauma that was either an isolated phenomenon or was associated with an injury not jeopardizing survival; eight spleens were salvaged. Mean intra-abdominal blood loss was approximately 1250 mL and, using a "cell saver," an average of approximately 790 mL was reinfused. Six received no other blood transfusion whereas three received 2250 mL homologous blood in addition to 4250 mL via the "cell-saver." With hilar laceration, repair was facilitated by temporarily occluding the splenic pedicle atraumatically, and suturing torn polar branches via the laceration site. In both children and adults with major splenic injury, the authors now recommend early laparotomy with reinfusion of autologous blood. The spleen or a large remnant can usually be salvaged, and homologous blood transfusion with its attendant complication can often be obviated altogether.

[Subjective sequelae of splenectomy]. / Die subjektiven Folgen des Milzverlustes.

111 of 806 former patients splenectomized at the Würzburg university hospital during the years 1968-1983 were interviewed for their complaints since their operation. Investigations included the use of Beck's inventory for measuring depression and the Giessen questionnaire for the evaluation of general complaints used in psychosomatic medicine. There was a significant increase of symptoms after splenectomy as compared to the normal population. A special list of 18 questions to investigate typical postsplenectomy complaints was answered by 95 of these 111 persons and by a control group of "statistical twins" with similar upper abdominal surgery without splenectomy. The leading difference was the highly significant increase of the susceptibility to infections after splenic loss followed by accelerated exhaustion and increased physical and mental weakness. The distribution of other complaints like for instance the intolerance to alcohol hitherto judged as typical sequelae of splenectomy was not statistically different in both splenectomy was not statistically different in both groups. Since the symptoms listed above as significantly increased in the splenectomized patient were closely correlated with the susceptibility to infection they seem to be rather the expression of the decreased resistance than direct consequences of the loss of the spleen.