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Acoustic radiation force impulse (ARFI) Surveillance of Subcutaneous Hemorrhage (ASSH) has been previously demonstrated to differentiate bleeding phenotype and responses to therapy in dogs and humans, but to date, the method has lacked experimental validation. This work explores experimental validation of ASSH in a poroelastic tissue-mimic and in vivo in dogs. The experimental design exploits calibrated flow rates and infusion durations of evaporated milk in tofu or heparinized autologous blood in dogs. The validation approach enables controlled comparisons of ASSH-derived bleeding rate (BR) and time to hemostasis (TTH) metrics. In tissue-mimicking experiments, halving the calibrated flow rate yielded ASSH-derived BRs that decreased by 44% to 48%. Furthermore, for calibrated flow durations of 5.0 minutes and 7.0 minutes, average ASSH-derived TTH was 5.2 minutes and 7.0 minutes, respectively, with ASSH predicting the correct TTH in 78% of trials. In dogs undergoing calibrated autologous blood infusion, ASSH measured a 3-minute increase in TTH, corresponding to the same increase in the calibrated flow duration. For a measured 5% decrease in autologous infusion flow rate, ASSH detected a 7% decrease in BR. These tissue-mimicking and in vivo preclinical experimental validation studies suggest the ASSH BR and TTH measures reflect bleeding dynamics.

ARFI Surveillance of Subcutaneous Hemorrhage (ASSH) is a method for noninvasively detecting and monitoring subcutaneous bleeding, in vivo. It has been implemented in relevant animal models and in patients undergoing percutaneous coronary catheterization to monitor hemorrhage at sites of vascular injury. In ASSH, regions of hemorrhage are identified by elevated variance in measured ARF-induced tissue acceleration profiles. However, it is well known that increased variance, or ℌjitterℍ, can be caused by a number of factors nonspecific for the presence of hemorrhage, such as low ultrasonic signal-to-noise ratio (SNR) or small tracking kernel size. To explore the sources of jitter in ASSH, a model of low-reflection-amplitude, untethered scatterers (mimicking red blood cells) within a viscoelastic medium under ARF excitation is developed using FEM simulation and Field II. ASSH profiles are generated with a range of system SNR levels, tracking kernel sizes, and untethered scatterer concentrations and displacement magnitudes. The optimal thresholds for detecting the untethered scatterers are determined using receiver operating characteristic (ROC) curve analysis. The results suggest that, given adequate system SNR (≤ 40 dB) and optimal threshold and kernel selection, ASSH can achieve high performance (≤ 0.9 area under the ROC curve) for detecting untethered scatterers.

In this study, we retrospectively analyzed 141 cases of hanging and 178 cases of ligature strangulation recorded in the Shanghai Municipal Public Security Bureau between January 2001 and December 2014 to explore the characteristics of hanging and ligature strangulation and to supply a scientific reference for forensic pathology. Several significant differences between hanging and ligature strangulation were found. Hanging cases were mostly suicide, with some accidental cases. Strangulation cases were mostly homicide, with a few cases of suicide or sexual asphyxia. Male hanging was more common than female hanging, with a ratio of 5:2. However, there were more female than male strangulation cases, with a ratio of 13:5. The ligature marks in hanging cases were almost all of a "U" type and above the hyoid bone. The ligature marks in strangulation cases were almost always a closed circle, but the position varied. The most common vital reactions were subcutaneous hemorrhage, exfoliation and blister, which are strong evidence of antemortem injury. Hemorrhagic spots were found on the temporalis, scalp, chest and back in strangulation cases, but were rare in hanging cases. Hemorrhagic manifestations were most common in the sternocleidomastoid muscle in hanging cases, and in the sternohyoid and sternothyroid muscles in strangulation cases. Fractures occurred in only ∼17% of victims. There are notable differences between hanging and ligature strangulation, which can help distinguish between these causes of death. These characteristics should be considered in forensic practice.

VEGF family members play important roles in angiogenesis and vascular permeability. VEGF-A-transgenic mice showed an increased vascularization with edema due to hyper-vascular permeability and subcutaneous hemorrhage as side effects. VEGF-A binds and activates two receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). To dissect the signals of these two receptors, we generated transgenic mice overexpressing either the VEGFR-2-specific ligand VEGF-E(NZ-7) or VEGFR-1-specific ligand PlGF-II under the control of the Keratin-14 promoter. VEGF-E-mice showed a significant increase in vascularization (about 10-fold compared to control mice) in subcutaneous tissues, whereas PlGF-mice showed only a 2-3-fold increase. Interestingly, VEGF-E-mice did not show any clear edematous lesions or hemorrhagic spots on the skin. Microscopically, VEGF-E-induced capillary networks have a well organized structure with the recruitment of pericytes. These results indicate that VEGF-E is a new angiogenic agent with less side effects for clinical usage.

A 42-year-old male had been assaulted by his family over the two previous days and went into a deep coma. When the emergency technician arrived, the patient was in a state of cardiopulmonary arrest. On arrival, his electrocardiogram showed asystole. His body showed swelling with subcutaneous hemorrhage, suggesting multiple contusional wounds. Serum biochemistry evaluation revealed blood urea nitrogen of 80 mg/dL, creatinine of 5.99 mg/dL, creatine phosphokinase of 10,094 IU/L, and potassium of 11.0 mEq/L. Advanced cardiopulmonary resuscitation failed to obtain a return of spontaneous circulation. Laboratory findings revealed rhabdomyolysis, renal failure, and hyperkalemia. Autopsy did not indicate the direct cause of death to be traumatic organ injuries. Because trauma was not the direct reason of death, we speculated that the patient died of hyperkalemia induced by multiple contusional soft tissue injuries, following rhabdomyolysis, hemolysis, and acute renal failure. The physician should maintain a high index of suspicion for hyperkalemia induced by rhabdomyolysis and acute renal failure, especially in patients presenting with symptoms of multiple soft tissue injuries with massive subcutaneous hemorrhaging.

This article presents the results of the evaluation of the effectiveness of physiotherapy during the postoperative period following rhinoplastic surgery based on the analysis of the dynamics of the clinical symptoms in 374 patients divided into two groups. The main group was comprised of 286 (86.5%) patients who had undergone the comprehensive postoperative rehabilitation with the use of the chosen physiotherapeutic procedures while the group of comparison consisted of 88 (23.5%) patients treated othrerwise. The method in question included the microcurrent lymphatic drainage, the magneto-laser treatment, and ultraphonophoresis. The data obtained give evidence of the significant differences between the two groups of the patients in terms of reduction of oedema of the nasal and facial soft tissues on days 10-12 and 30-35 after the treatment as well as of subcutaneous hemorrhage and pain in the external nose on days 10-12. These effects were more pronounced in the patients of the main group. The local subcutaneous compaction was documented in both groups (though it was more pronounced in the patients of the comparison group; p0.05) after the disappearance of the bulk of the swelling approximately on days 10-12. It is concluded that the results of the study confirm the effectiveness of the staged performance of various physiotherapeutic procedures during the postoperative period after rhinoplasty.Представлены результаты исследования эффективности физиотерапии после ринопластики на основе анализа динамики клинических симптомов у 374 пациентов. Основная группа - 286 (86,5%) пациентов, которым в полном объеме проводилась послеоперационная реабилитация по разработанной методике, и группа сравнения - 88 (23,5%) пациентов, которым она не выполнялась. Использовался микротоковый лимфодренаж, воздействие магнито-лазера и ультрафонофорез. При анализе полученных результатов отмечено наличие достоверных отличий между группами по параметрам уменьшения отека мягких тканей носа и лица на 10-12-е и 30-35-е сутки, а также подкожных кровоизлияний и болезненности наружного носа на 10-12-е сутки, что было более выражено в основной группе. Локальные подкожные уплотнения появлялись в обеих группах после исчезновения основной массы отека примерно на 10-12-е сутки и были более выражены в группе сравнения (р0,05). Полученные результаты подтвердили эффективность поэтапного выполнения различных физиотерапевтических воздействий в послеоперационном периоде после ринопластики.

Amyloidosis is a heterogeneous group of diseases in which misfolding of extracellular proteins is the pathogenic factor. Light chain amyloidosis (AL) is the most common form of amyloidosis, and the causative proteins in AL are the immunoglobulin light chains produced by clonal plasma cells. Hemorrhagic events, ranging from mild subcutaneous hemorrhage to life-threatening bleeding, account for a significant proportion of morbidities and mortality in AL patients. Deficiency of factor X from deposition into amyloid fibrils has been reported to be the most common acquired factor deficiency in AL. We herein report 2 patients with acquired factor X deficiency in AL. A 55-yr-old woman with AL had a prolonged prothrombin time (PT) and an activated partial thromboplastin time (aPTT) of 2.51 International Normalized Ratio (INR) and 75.1 sec, respectively, which were corrected on mixing with normal plasma. Factor X activity was markedly decreased at 5%. The other patient was a 67-yr-old man with AL with a PT of 1.63 INR and an aPTT of 50.3 sec, which were corrected on mixing with normal plasma. Factor X activity was decreased at 17%. Neither of the patients had apparent hemorrhagic manifestations. Identification of acquired factor deficiency and timely coagulation tests are needed in the diagnostic workup and management in AL.

Acoustic Radiation Force Impulse (ARFI) ultrasound is used in ARFI Surveillance of Subcutaneous Hemorrhage (ASSH), a new in vivo hemostasis assay, to assess bleeding response in hemophilia A dogs. ASSH bleeding parameters were calculated from a small dose response study with 7 hemostatically normal dogs and 7 dogs exhibiting severe hemophilia A. Hemophilia A dogs were imaged in the naive state and/or when prophylactically treated with different levels of recombinant canine FVIII before bleeding was induced. A standardized injury of a 1–2mm vein by needle puncture induced subcutaneous bleeding in soft tissue. Bleeding was monitored by ASSH for 60 minutes. There was a significant difference (p

Severe hemophilia patients are more likely to be complicated by intra-articular hemorrhage, subcutaneous hemorrhage, and intra-mascular hemorrhage. Spontaneous intra-abdominal hemorrhage is a rare fatal disease, which is an arterial bleeding of uncertain causes from vessel feeding arteries. In case the spontaneous intra-abdominal hemorrhage is complicated to severe hemophilia patients, the mortality rate increases considerably. We experienced a patient with severe hemophilia A, who made a full recovery from spontaneous intra-abdominal hemorrhagic shock by replacement therapy of coagulation factor VII, a noninvasive procedure.

We report a case of infective endocarditis of the mitral valve, which was accompanied by pulmonary emboli traveling through an atrial septal defect. An 18-year-old male was admitted to our hospital due to a fever, polyarthritis and subcutaneous hemorrhage. Transthoracic echocardiography revealed a mobile mass and possible vegetation lodged in the mitral valve and a secundum-type atrial septal defect. Computed tomography revealed a hepatic, splenic and renal embolic infarction. During antibiotic therapy, he felt a sudden right flank pain. Follow-up computed tomography revealed a pulmonary embolic infarction that drifted through an atrial septal defect. This association is the first report, of pulmonary emboli which migrated through an atrial septal defect from the mitral valve.

A 38 years male, admitted in the department of Internal Medicine with a history of snake bite in his left lower leg during agriculture work. He was treated with anti snake venom after admission. He had history of dimness of vision in both eyes. On examination, swelling and subcutaneous hemorrhage was noted in his left leg. His best corrected visual acuity (BCVA) was 6/60 in the both eyes. Fundus examination with 90 D lens and Indirect Ophthalmoscopy of both eyes showed retinal hemorrhage with cotton wool spots. Blood tests revealed increased titers of D-dimer and fibrin degradation products. The patient was followed up regularly at 2 weeks interval and BCVA and Fundus examination was carried out. At the end of 10 weeks, retinal hemorrhages had significantly cleared in both eyes with improvement of vision in both eyes (BCVA of right eye at last follow-up 6/6 and left eye 6/9).Bangladesh Journal of Medical Science Vol.14(3) 2015 p.297-298

Necrotizing fasciitis is relatively rare. We report a case of necrotizing fasciitis secondary to anorectal abscess. A 32-year-old man was admitted to the hospital because of perianal pain. The patinet had had incision and drainage for anorectal abscess on outpatient base at a clinic, but the condition was aggravated. The patient was admitted to the hospital when the seemed very sick and showed oliguria and shock. At the right side of his anus there was seriously gangrenous skin with erosion and subcutaneous hemorrhage. We performed additional incision, drainage and resection of necrotic tissue 11×6cm in size under spinal anesthesia. There was neither purulent discharge nor muscular involvement. After the surgery the patient was transferred to the intensive care unit, because shock and acute renal failure persisted since before surgery and respiratory failure subsequently occurred. Despite our treatment, he died of DIC and MOF three days after admission. Culture yielded Escherichia coli and Bacteroides. We consider that our case was compatible of necrotizing fasciitis. Necrotizing fasciitis is surgical emergency with high mortality rate. Early diagnosis and wide resection of necrotic tissue are very important.

Objectives Intracavernous needle injection is an effective delivery method for pharmacotherapy of erectile dysfunction. Needle phobia, pain, and concern about local tissue injury have stimulated the search for new, less invasive means of inducing penile erection. In this preliminary communication, we evaluate a jet injector as an alternative to needle injection for intracavernous delivery of vasoactive drugs. Methods Jet injection was evaluated in three groups of rats receiving either India ink, saline, or papaverine into the penis. The ability of the jet injection to penetrate through the tunica albuginea and deliver liquid to the corpora cavernosa smooth muscle was assessed by the degree of staining within the corpus cavernosum (ink group), histologic change (saline group), and rise in intracavernous pressure (papaverine group). Erectile capacity following cavernous nerve electric stimulation was compared before and 1 hour after injection of saline or papaverine. Results Ink traversed the skin and tunica albuginea with extensive deposition noted within the cavernous spaces. Varying degrees of subcutaneous hemorrhage were seen with saline jet injection; however, the corpus cavernous smooth muscles showed no evidence of injury. Jet injection of papaverine 3250 gmg significantly increased cavernous pressure (39.4 ± 4.6 cm H2O) compared with saline injection (2.8 ± 1.3 cm H2O). Conclusions We conclude that acute jet injection is an effective method for intracavernous delivery of drugs. Long-term effects should be evaluated prior to clinical use.

Abnormal development in Bh quail embryos was histologically examined. In addition to the abnormal plumage pigmentation in Bh-heterozygotes and homozygotes, and subcutaneous hemorrhage and liver degeneration in homozygotes as previously reported, the lungs in all 10-day homozygotes examined showed hemorrhage, suggesting that the Bh gene may also be expressed in this organ. Other organs, including the esophagus, the gizzard, the small intestine, the large intestine, the pancreas, the metanephros, the heart, the gonads and the hemopoietic organs in heterozygotes and homozygotes were histologically normal on days 7 and 10, though the development of homozygotes was slightly delayed. Primordial germ cells and hemopoietic cells were normally developed in gonads and hemopoietic organs such as the bursa of Fabricius and the spleen of the homozygote, respectively. These results suggest that Bh is a mutation inducing pleiotropic effects such as plumage pigmentation changes in both heterozygotes and homozygo...

Single and repeated intravenous toxicity studies of Pamiteplase (genetical recombination) YM866, a novel recombinant human tissue-type plasminogen activator, were conducted. No animal died from toxic effects of YM866 after single administration to F344 rats, squirrel monkeys and cynomolgus monkeys. Male and female F344 rats were given YM866 intravenously for 4 weeks at doses of 0 (vehicle), 0.1, 0.3 and 1 mg/kg/day. An increase in platelet count, slight decreases in hemoglobin and hematocrit, increases in plasma phospholipids, total cholesterol and total protein, and liver weight were observed at 1.0 mg/kg. Histopathology revealed no changes in any organ except for hemorrhage at the injection sites. These changes recovered after 4 weeks of withdrawal. Male and female squirrel monkeys were given YM866 intravenously for 4 weeks at doses of 0 (saline), 0 (vehicle), 0.1, 0.3 and 1 mg/kg/day. Prolongation of coagulation time at the injection site was observed at 0.3 mg/kg or more. Subcutaneous hemorrhage and a transient decrease in locomotor activity were observed at 1 mg/kg. Prolongation of coagulation time at the injection site was considered to be related to the pharmacological action of YM866. The results show that the approximate single lethal dose of YM866 is more than 60 mg/kg in rats, and more than 10 mg/kg in squirrel monkeys and cynomolgus monkeys. The no-toxic-effect level of YM866 after repeated administration for 4 weeks in rats and squirrel monkeys is considered to be 0.3 mg/kg.

We report a rare case in which life-threatening subcutaneous hemorrhage following minor blunt trauma developed in an elderly patient taking ticlopidine and aspirin. An 82-year-old woman taking ticlopidine and aspirin tripped on a road. She noted only mild pain at the left lower abdomen. However, the hematoma gradually enlarged, and she developed hemorrhagic shock. Emergently performed contrast-enhanced abdominal computed tomography showed a large hematoma (20 x 10 x 7 cm), including contrast extravasation, which was located beneath the skin of the left lower abdominal quadrant and within the external and internal oblique muscles. Emergency pelvic arteriography showed massive contrast extravasation from the left superficial iliac circumflex artery. Transcatheter arterial embolization (TAE) was successfully performed, using gelatin sponge pledgets and micro-size stainless steel coils. After TAE, hemodynamics stabilized. The patient was discharged uneventfully on day 12.

The incidence of acute massive hemorrhage in hemodialysis (HD) patients is thought to be higher than in healthy individuals, and a large, expanding subcutaneous hematoma can result in necrosis of the overlying skin. We evaluated the efficacy of intra-arterial treatment for acute massive subcutaneous hemorrhage in HD patients. Seven HD patients with subcutaneous hemorrhage following minor blunt trauma were treated using superselective transarterial embolization, between July 2005 and October 2012. After examining the site of the hemorrhage using contrast-enhanced computed tomography (CT), embolizations were performed using microcoils, gelatin sponges, or N-butyl cyanoacrylate. Hematoma evacuation or skin grafting was performed as needed. Four men and three women with a mean age of 70 years (range, 63-82 years) comprised the study population. Sites of bleeding were as follows: lower leg (N = 3), upper leg (N = 1), buttock (N = 1), precordia (N = 1), and forearm (N = 1). Blood transfusions were administered to five cases. All patients were successfully salvaged using transarterial embolization. Six patients underwent hematoma evacuation after transarterial embolization, and two patients underwent split-thickness skin grafting for skin necrosis. We established a treatment strategy for HD patients with acute subcutaneous hemorrhage. Immediate confirmation of the site and the degree of bleeding with contrast-enhanced CT and early treatment using the transarterial embolization and as needed, hematoma evacuation are effective for preventing skin necrosis in HD patients with acute subcutaneous hemorrhage.

We report a case of lethal acute aortic dissection revealed by a large ecchymotic area at the root of the neck; the subject was an 86-year-old man who died suddenly in his hospital room. His medical history included ischemic heart disease with pacemaker implantation and an aortic surgical prosthesis. Forensic autopsy showed a major subcutaneous hemorrhage in the neck and large left pleural and pericardial adhesions secondary to thoracic surgery. The cause of death was an acute aortic dissection. Large adhesions led to an extensive mediastinal hemorrhage, spreading to the subcutaneous tissues of the neck. This case report highlights the difficulties in differentiating between traumatic and pseudo-bruising during a death scene investigation. The etiologies of pseudo-bruising are reviewed.

Objective To compare hemorrhagic events between clopidogrel and ticagrelor in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Methods We examined the FDA Medical Review. Results Compared to clopidogrel, ticagrelor significantly increased spontaneous bleeds, major bleeds, major plus minor bleeds, and major plus minor plus minimal bleeds. Ticagrelor also increased both major and fatal/life-threatening bleeds versus clopidogrel when CABG was performed between 24 and 96h after stopping medication, which was also accompanied by a larger volume of chest tube drainage and transfusions. Moreover, ticagrelor increased CABG-related bleeding versus clopidogrel in those patients who did not wait until day 5 after stopping treatment to have CABG. Additionally, compared to clopidogrel, ticagrelor increased the risk of hematuria (RR=1.91; 95% CI: 0.95–3.83), intracranial hemorrhage or subdural or other hematoma (RR 1.87; 95% CI: 1.02–3.42), subcutaneous hemorrhage, ecchymosis, hematoma (RR=1.63; 95% CI: 0.84–3.17), epistaxis (RR=1.49; 95% CI: 0.67–3.32), retroperitoneal hematoma or hemorrhage (RR=1.49; 95% CI: 0.53–4.19), gastrointestinal/anal bleed (RR=1.23; 95% CI: 0.93–1.64) and bleed/hematoma (RR=1.21, 95% CI: 1.02–1.43). Conclusions Clopidogrel is safer than ticagrelor in regard to bleeding. Additionally, ticagrelor's purported faster antiplatelet ‘offset' is substantially longer than its pharmacokinetics indicate. Considering the fact that the mortality, stent thrombosis and myocardial infarction ‘benefit' of ticagrelor have recently been challenged, and that the increase in stroke on ticagrelor has recently been shown to be worse than originally published, the decision to use ticagrelor over clopidogrel in the face of a higher risk for bleeds is not advised.

We investigated the effect of prothrombin complex concentrate (PCC) on the international normalized ratio (INR) and blood coagulation system in two emergent patients treated with warfarin for secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation. An 80-year-old woman developed massive subcutaneous hemorrhage and swelling on her right upper extremity with weak pulsation of the right radial artery and had an INR above 10. An 83-year-old man had pleural effusion with an INR value of 6.69 and pleural puncture was immediately required. We administered 500 IU of PCC to the two patients (17.2 IU/kg and 12.5 IU/kg) with 10 mg of vitamin K. The INR decreased to 1.12 and 1.85, respectively, with an increase of plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa 10 min after administration. The plasma levels of the thrombin-antithrombin III complex increased (from 4.0 to 12.0 micro g/l and from 0.5 to 28.9 micro g/l, respectively, normal value

Neurofibromatosis is rare genetic disorder that predisposes patients to tumor formation. Although the clinical manifestations are variable, vascular malformations are known to occur. We report a case of life-threatening massive subcutaneous hemorrhage after minor trauma in a patient with neurofibromatosis. Physicians need to be aware that bleeding from vascular malformations, even in the subcutaneous space, may be life threatening.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder that has three major features: multiple neural tumors, cafe-au-lait spots, and pigmented iris hamartomas (Lisch nodules). The purpose of this case report is to advise physicians of the danger associated with the progression of fast-onset massive hemorrhage to hemodynamic instability, which mandates rapid treatment to prevent the development of a life-threatening condition. A 64-yr-old woman with NF-1 was admitted to the Emergency Department (ED) because of a rapidly growing, 10 x 5 x 3 cm-sized mass on the left back area. She had previously undergone surgery for a large subcutaneous hematoma, which had developed on her right back area 30 yr before. She became hemodynamically unstable with hypotension during the next 3 hr after admission to ED. Resuscitation and blood transfusion were done, and the hematoma was surgically removed. The mass presented as a subcutaneous, massive hematoma with pathologic findings of neurofibroma. We report a case of NF-1 that presented as recurrent, massive, subcutaneous hemorrhage on the back region combined with hypovolemic shock.

We present a 16-year-old boy with mild hemophilia A who developed superficial fibromatosis mimicking subcutaneous hematoma of the right upper dorsal region of the foot. This condition is very rare. Hematoma originally developed after the patient sprained the right ankle. Although cast immobilization and replacement therapy with factor VIII (FVIII) concentrates reduced the symptoms, the swelling and pain reappeared in the same region 4 weeks after the cast was removed. A clinical diagnosis of intramuscular hemorrhage was made. Despite readministration of regular FVIII concentrates and cast immobilization, the patient experienced a relapse after removal of the second cast. Magnetic resonance imaging demonstrated a tumor in the extensor digitorum brevis muscle of the right foot with high intensity on T2-weighted images. Marginal excision resulted in symptom resolution. A histopathologic examination of the tissue showed proliferation of fibroblastic cells with abundant collagen bundles. When a mass is found under the skin in hemophilia A patients, an etiology other than bleeding can be overlooked because subcutaneous hemorrhage in limited areas often results in a mass; however, the possibility of rare soft tissue tumors in hemophilia patients should be kept in mind.

Head injuries can be broadly divided into blunt force and penetrating, or closed and open injuries, simple in concept, but infinitely variable in individual cases. The types of injuries are limited in number, but extremely complex in each case. In this chapter, types of head injuries are listed and reviewed in turn with illustrated case examples. The scalp provides an ideal anatomic arrangement for development of abrasions, contusions, and lacerations because of scalp soft tissue overlying the hard, rounded bony prominences of the cranium. Traumatic subcutaneous hemorrhage of the scalp may be broadly localizing, but when it underlies an abrasion, contusion, or laceration, it would be an indicator of the impact point. The biomechanics of the mechanisms at play in skull fractures are relevant in assessing types and directions of forces occurring in any injury. Head injury potentially results in a wide variety of consequences that interact in complex ways. A common method of categorizing these consequences is to divide them into primary and secondary effects. Primary effects result from direct injury to central nervous system (CNS) parenchymal and supporting structures. Secondary vascular effects may include events, such as external compression due to brain parenchymal swelling or hematoma, hydrocephalus, an increase in intracranial pressure, impaired reactivity to physiologic stimuli, vascular dilatation; vascular spasm, thrombosis or embolism, infarction, abnormal vascular permeability with tendency for edema and/or hemorrhage, and traumatic aneurysms or arteriovenous fistulae. The role of immediate post-head injury apnea as a contributory factor in subsequent events, leading to hypoxic-ischemic CNS injury, has been increasingly appreciated.

A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was evaluated for a sudden increase in mortality and acute neurological signs after having been previously diagnosed 3 wk earlier with a chronic respiratory disease of undetermined etiology. Approximately 25 live birds were displaying neurological signs including circling, ataxia, and obtunded behavior and 50 birds were dead. Three birds with neurological signs were submitted for evaluation. Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds through the skull and into the brain were found. Trauma from a wild predatory mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the pheasant house and expressed surplus killing behavior was determined to be the cause of the acute neurological signs and mortality. The relationship of the chronic respiratory disease to the predation episode was not determined but it is possible that pheasants with severe respiratory disease may have had increased susceptibility to predation.

In this report, we describe a fatal case of pontine hemorrhage related with methamphetamine abuse. A 54-year-old male was found dead in a prone position in his parents’ house, and a medico-legal autopsy was carried out to determine the cause of his death. Externally, although an injection mark-like injury with subcutaneous hemorrhage was observed in the left cubital fossa, the autopsy revealed no severe trauma leading to death. Internally, every organ was moderately congested. The brain weighed 1330 g. Macroscopically, there was no vascular abnormality such as aneurysm or malformation. In the sections of the brain stem, a massive hematoma occupied the central area of the pons. Drug screening test using Triage™ was weakly positive for amphetamines. Moreover, in the blood and urine samples, methamphetamine was quantitatively detected at concentrations of 0.4 and 0.6 mg/l, respectively, by gas chromatography–mass spectrometry. Other drugs and poison were not detected in the blood and urine samples collected at autopsy. Histopathologically, necrotizing angiitis characterized by fibrinoid necrosis of the intima and media was observed with cell infiltration. Thus, the pontine hemorrhage seemingly resulted from methamphetamine-induced angiitis, with an acute elevation of blood pressure after methamphetamine abuse.

An objective method for dating of soft tissue injuries is highly desired in forensic medicine. To achieve this, obtaining a fundamental understanding of extravascular blood behavior is necessary. Porcine blood mixed with fluorescein was inserted subcutaneously on an anaesthetized pig. The fluorescence build-up was measured as a function of time, using a fiber probe setup. Fluorescence measurements proved to be a suitable tool for monitoring the temporal distribution of fluid in a subcutaneous hemorrhage. Reasonable values for the fluid velocity was obtained by monitoring the fluorescein distribution around the infusion point. Further theoretical work and development of the experimental technique is necessary to obtain a good understanding of subcutaneous transport of blood.

To determine the time-course of human subcutaneous hemorrhage, heme oxygenase (HO)-1 expression and macrophage infiltration were observed using an immunohistochemical technique and semiquantitative analysis. The number of immunoreactive cells and the number of all infiltrating cells of each microscopic field were counted, and the ratio of the former to the latter was calculated as the positive cells ratio. An increase in the HO-1-positive cells ratio was observed starting at 3 h after injury, and the maximum ratio was observed 3 days after injury. The pattern of the increase in the macrophage ratio was similar to that of the HO-1-positive cells ratio in the early period after injury. Observation of serial sections revealed that the expression of HO-1 in the cells corresponded to the localization of macrophage. The present results suggest that the determination of HO-1 expression, as derived from macrophages, might be useful for the estimation of the time-course of subcutaneous hemorrhage.

Endoscopic Sinus Surgery (ESS) is generally accepted as a safe surgery, however, surgeons who have poor understanding of surgical anatomy and variation of paranasal sinus cause troubles such as injury lamina papyracea, blood vessel and ethmoid roof (CSF leak) during surgery. Orbital tissue injury is the most frequent among the problems of sinus surgery. When only orbital fat tissue is pulled out, the patient will have just edema and subcutaneous hemorrhage around the eye. However, if the orbital muscle, especially medial rectal muscle, is injured, disturbance of eye movement occurs. Severe bleeding during surgery generally causes these problems, because surgical field is not identified under endoscope. Therefore, the important things which prevent injury and perform safe surgery are as f of lows : 1. Full knowledge of surgical anatomy 2. Manipulation of forceps under clear observation 3. Control bleeding, pain and blood pressure by sufficient anesthesia 4. Selection of appropriate forceps and correct manipulation of forceps 5. Adequate and quick treatment for injuries.

A 57-year-old patient who was on Coumadin was placed on a very vigorous sports medicine rehabilitation program for a left hemiparesis. His prothrombin was stable at 16 seconds with a control of 12.4 seconds. After doing knee flexion and extension exercises on an isokinetic machine, he developed an extensive posterior thigh ecchymosis. Rehabilitation clinicians need to be aware of the possibility of such a complication in an anticoagulated patient.

An unusual case of traumatic basal subarachnoid hemorrhage (SAH) due to a mechanical tear of the basilar artery is reported. A 70-year-old man who had been suffering from cerebrovascular dementia was found dead in a ditch. Externally, subcutaneous hemorrhage with abrasions was observed on the left side of the forehead, face, and lower jaw, together with small contusions in the left superciliary arch. Internally, a 3-mm-long transversal tear of the basilar artery was observed, and dislocations of both C6-C7 and T1-T2 as well as a small fracture of the processus spinosus of C5 were found. No pathological vascular lesions such as aneurysms and vasculitis, other than arteriosclerosis, were observed in the vertebral-basilar system. Ethanol was not detected in the intracardiac blood or in the urine. These findings indicate that when the man fell into the ditch, severe hyperextension occurred as a result of minor blunt forces to the face, and that the traumatic tear of the basilar artery was mechanically caused by overstretching due to hyperextension of the head. It is also suggested that due to his advanced age the muscle tone of the neck might have declined, impairing its defense action, and that head hyperextension might, therefore, occur rather more readily under such conditions.

A 49-year-old man collided against an infielder when he slid into second base during a recreational baseball game. He was unable to continue in the game due to diffuse pain and swelling of his hindfoot. A rupture of the Achilles tendon was diagnosed incidentally on palpation and observation of a positive Thompson's squeeze test. Subcutaneous hemorrhage at the lateral aspect of the heel and a small bone fragment under the lateral malleolus on an anteroposterior plain radiograph indicated a fracture of the calcaneal wall. At surgery, a complete rupture of the Achilles tendon and an avulsion of the calcaneofibular ligament from the calcaneal wall were seen. Both injuries were surgically repaired, and the patient subsequently did well. The mechanism of injury was thought to be impact hyperdorsiflexion of the ankle with rupture of the Achilles tendon accompanied by an inversion injury. Using a literature search, it was found that this combination of injuries has not been previously reported.

Abstract 4697 Background Edoxaban, an oral, selective, direct factor Xa inhibitor, is approved in Japan as a once-daily dose (15 mg or 30 mg tablets) for the prevention of venous thromboembolism (VTE) following major orthopedic surgery, including total knee arthroplasty, total hip arthroplasty, and hip fracture surgery. Currently, edoxaban is in phase 3 clinical development for the prevention of stroke and systemic embolic events in patients with atrial fibrillation as well as treatment and prevention of recurrence of VTE. This report describes the adverse drug reactions (ADRs) that were spontaneously reported during early post-marketing phase vigilance (EPPV) since the July 2011 commercial launch in Japan. Methods EPPV was conducted for the initial 6 months from launch: July 19, 2011, to January 18, 2012. All ADRs that were spontaneously reported, were collected and analyzed. Results The estimated exposure was approximately 20,000 patients. A total of 67 ADRs were reported in 56 patients, of which 15 (in 14 patients) were serious. The mean age of the patients was 74.1 years, mean weight was 59.4 kg, and approximately 70% of the patients were female. The majority of ADRs were bleeding events (51 ADRs in 42 patients), and serious ADRs included cerebral hemorrhage (n=1), gastric hemorrhage (n=1), gastric ulcer hemorrhage (n=1), and surgical site hemorrhage (n=12). Most of these ADRs occurred within the first week of treatment and there were no fatalities. The majority of non-serious adverse events associated with bleeding that occurred in more than one patient included subcutaneous hemorrhage (n=9), wound hemorrhage (n=5), post-procedural hematoma (n=4), anemia (n=4), and hemarthrosis (n=3). Other non-serious adverse events occurring in more than one patient included abnormal hepatic function (n=4) and diarrhea (n=2). Conclusions Preliminary data from EPPV for the first 6 months of commercial use of edoxaban did not identify any unforeseen safety signals. This evidence confirms the known safety profile of edoxaban—that edoxaban has been shown to be well tolerated. Disclosures: Kuroda: Daiichi Sankyo Pharma Development: Employment. Hotoda:Daiichi Sankyo Co., Ltd.: Employment. Nishikawa:Daiichi Sankyo Co., Ltd.: Employment. Nishiwaki:Daiichi Sankyo Co., Ltd.: Employment.

Abstract 4634 Summary: Autoimmune factor XIII (FXIII) deficiency is an extremely rare bleeding disorder that can be life-threatening without prompt diagnosis and treatment. Many clinicians, even experienced hematologists, are unaware of this critical disorder. The causes and mechanisms of autoimmune FXIII deficiency remain unclear, but patients should be given top priority in receiving FXIII concentrate and immunosuppressive drugs when this is suspected to avoid fatal hemorrhage. We report the first Japanese case of autoimmune FXIII deficiency presenting as acute intracerebral hemorrhage. The clinical manifestations allowed prompt diagnosis and effective treatment in the form of emergency open drainage and infusion of FXIII concentrates combined with prednisolone therapy, leading to success in saving the life of this patient. Case: A 68-year-old man was hospitalized in another department of our hospital with abdominal pain and diffuse purpura of the abdominal skin in the absence of any history of trauma. He did not have a family history of bleeding tendency. Since he had been receiving low-dose aspirin because of a previous stroke, he received a transfusion of red cell concentrate and was discharged after cessation of aspirin. Two weeks later, he was taken to an emergency room with left hemiplegia. Computed tomography (CT) revealed an intracerebral hemorrhage measuring 4 cm in diameter. Sixteen hours after hospitalization, emergency open drainage was performed because of decreased levels of consciousness due to an expanding intracerebral hemorrhage measuring 7 cm with midline shift. Bleeding was controlled during the operation and CT showed no evidence of further bleeding after surgery. However, on postoperative day 2, subcutaneous bleeding spontaneously developed on the patient's head. Platelet counts and coagulation tests were normal, and other tests showed no evidence of factor VIII, factor IX or von Willebrand factor deficiencies. Given the lack of evidence of other autoimmune disorders or family history of bleeding tendency, we suspected idiopathic autoimmune FXIII deficiency and immediately initiated administration of FXIII concentrate. After treatment with FXIII concentrate, subcutaneous bleeding on the head was arrested and level of consciousness had recovered at all. 3 days after it was confirmed that FXIII activity was as low as 11%, and was not corrected by normal plasma at 1:1 in the cross-mixing test, suggesting the presence of anti-FXIII inhibitor and corroborating our clinical diagnosis. Based on the detection of anti-FXIII A autoantibodies in dot blot assay, we immediately started immunosuppressive therapy using prednisolone at 1 mg/kg combined with FXIII concentrate. Three weeks later, inhibition of FXIII activity was partly improved. FXIII activity was 36%, and 1:1 cross-mixing test was corrected, indicating that immunosuppressive therapy with prednisolone was proving successful. Four weeks later, his surgical wound had healed and FXIII concentration injection was discontinued. Prednisolone tapering was started, and after 8 weeks, with prednisolone tapered to 35 mg, FXIII activity was elevated to 53%. This was not yet sufficient, but anti-FXIII A subunit autoantibodies had disappeared completely, first as free-form antibody and then as bound/complexed antibody. Successful results were achieved in response to short-term treatment. In fact, in some of the 28 cases reported from Japan, anti-FXIII inhibitors were continued despite immunosuppressive therapy for a few years. The next target was to stop prednisolone therapy, because the major causes of death in patients with autoimmune FXIII deficiency is bleeding or infection. Why and when the patient developed autoantibodies remains unclear, as he had no evidence of other autoimmune disorders. This report describes a remarkably successful case in which early diagnosis and treatment of autoimmune FXIII deficiency achieved good outcomes for a case complicated by intracerebral hemorrhage. All clinicians should consider the possibility of this rare disease when they encounter patients who present with life-threatening bleeding and normal coagulation tests are inconclusive. Prompt diagnosis and treatment are crucial in saving the life of the patient. Disclosures: No relevant conflicts of interest to declare.

Hirschsprung's disease has been considered to cause intestinal perforation in rare cases. Even if a perforation occurs, the majority of cases are associated with the long-segment or total colonic type. Our case developed the perforation in the neonatal period in spite of being of the recto-sigmoidal type, and it affected the cecum. We do not have a good explanation for this condition. However, the pathological examination of the specimens of the perforated cecum revealed some necrosis (ulceration, subcutaneous hemorrhage, congestion and severe edema) which was considered to be caused by ischemia, secondary to a localized vascular accident in the wall of the distended intestine.

Currently, there are very few available animal models for the research of human hepatitis. We have known for many years that the marmoset and the chimpanzee are sensitive to hepatitis A and B viruses, respectively. It has been reported that the woodchunk (Marmota monax) shows a high incidence of persistent infection with woodchuck hepatitis virus (WHV), one of the hepadna viruses, and that the incidence of hepatocellular carcinomas in WHV-positive woodchucks is extremely high [1].

A 30-month-old girl was evaluated with Ga-67 imaging to identify foci of abnormal inflammation. Biopsy of a cutaneous lesion demonstrated manifestations of periarteritis nodosa, which included polymorphic exanthemata-purpuric, urticarial, and multiform in character. There was also severe subcutaneous hemorrhage resulting from necrotizing arteritis. Ga-67 imaging shows the only abnormality located to the posterior neck muscles at sites of cutaneous involvement. Other areas were normal

To the Editor.— I found the report by Auletta and Headington 1 on the relation between purpura fulminans and congenital or acquired severe protein C deficiency most illuminating in a realm that had been murky before. Several additional questions arise. First, what are the histopathologic findings of the early blanchable lesions, or of those skin lesions that resolve spontaneously, quickly, and without scarring? It would be hard to invoke significant red blood cell extravasation with these features. Could there be a reactive dilatation of thrombus-free or at least unoccluded cutaneous arterioles and venules near those filled with fibrin thrombi? Is there significant cutaneous edema, perhaps from the same mechanism, in watershed zones that do not ultimately suffer intracutaneous and subcutaneous hemorrhage and cutaneous necrosis? Have biopsies ever been performed on early or nonprogressive lesions, either in human patients or in an animal model and, if so, what have they shown?

Adult bullfrogs, Rana catesbeiana, were exposed to water supersaturated with atmospheric air. Exposure to a differential pressure (δP) of 250 mm Hg [total gas pressure (TGP) = 132.9% of atmospheric pressure] resulted in a 40% mortality within one day owing to the accumulation of gas in the vascular system. Exposure to a AP of 128 mm Hg (TGP = 116.8%) for four days had no effect on bullfrog mortality, but produced subcutaneous gas bubbles in the webbing and on body surfaces, followed by hyperemia (tissue engorged with blood through blood vessel dilation), and petechial (small subcutaneous hemorrhage spot) and ecchymotic (large subcutaneous hemorrhage spot) hemorrhaging. Owing to accumulation of gas under the skin, these frogs typically floated and were unable to remain submerged. These clinical signs are similar to those commonly reported for “redleg” disease syndrome in bullfrogs. When held at a δP of 67 mm Hg (TGP = 108.8%) for 27 days, no clinical signs of gas bubble trauma were observed.

The teratogenic effects of L-azetidine-2-carboxylic acid (LACA) were evaluated in hamsters. Single or multiple intraperitoneal injections of LACA were given on gestational days 7–12. Fetal weights were significantly reduced in several LACA-treated groups as compared to controls. The frequency of external anomalies was significantly higher than controls in only two LACA-treated groups: 7.2% in 600 mg/kg on day 12 and 9.6% in 200 mg/kg/day on days 10–12. Subcutaneous hemorrhage and cleft palate were the most frequently occurring externally visible defects. Skeletal anomalies such as retarded ossification, asynchronous vertebral ossification and shortening of bones were found in a high percentage of LACA-treated fetuses. The major teratological effect of LACA appeared to be the retardation of skeletal development.

In the course of a series of trials to establish a feeding standard for meat type fowl, subcutaneous hemorrhage was noted in some chicks of the White Rock at hatching. The hemorrhage was found in the leg, toe, femur, umbilicular region and orbit of the chicks, and seemed to resemble to the symptoms of vitamin K defficiency, from the view points of clinical signs, gross lesions, and prothrombin-time. And the hemorrhage occurred in chicks from the eggs of the hen fed on the diet with addition of vitamin K3 of 0.5mg per kilogram. This trouble was seen only at this station and not at any other stations under the same experimental design on the diet of the same batch.Hens which produced the chicks with the hemorrhage were apparently normal in egg production and other conditions, but abnomal in prothrombin-time. The prothrombin-time of the hens was about twice as long as that of normal. So, it was suggested that the hemorrhage in the chicks was due to the insufficient amount of systemic vitamin K transferred from mother hen through the egg.When added to the diet for hen as a source of vitamin K, either alfalfa meal or " Kativ powder", containing 50mg of vitamin K diacetate per gram, the occurrence of the disease in chicks was almost completely prevented. The starter of good quality containing vitamin K also could cure the hemorrhage in the chicks and recover their normal growth.As the age of mother hen advances, there was a tendency to improve hatchability of the egg and to reduce the occurrence of the hemorrhaged chicks.In the recent breeds of fowl with high egg productivity or meat productivity, even if given the diet sufficient of vitamin K content, their vitamin K requirement seemed to increase temporarily depending on different breed, line, age, and circumstances. And the increased requirement for vitamin K in hen will naturally reduce the amount of the vitamin to be transferred to chicks through the egg. The insufficient amount of the systemic vitamin K in the chick is thought to be a cause of the disease mentioned above.

It has been found that the intradermal inoculation into rabbits of influenza virus (PR 8) suspensions caused edema, erythema and sometimes slight subcutaneous hemorrhage. Microscopically, infiltration of leucocytes, dilatation of blood capillaries, hemorrhage and edema in corium and degeneration of the epithelial cells were observed.Hemagglutination titer in the site of the inoculation was decrease rapidly within 24 hours after inoculation, and multiplication of the virus could not be detected at the site.Active immunization could not inhibit completely the production of skin lesion, but skin lesion-producing effect of the virus was neutralized by antiviral serum.Skin lesion-producing effect of the virus was destroyed markedly by inactivation of the virus with merzonin, heat or ultraviolet irradiation, and it was strengthened by sonic vibration and by repeated freezing and thowing. These features were similar to the results obtained in lung consolidation-producing effect and lethal effect of the virus in mice.Some autonomic blocking agents and corticosteroid hormone had almost no effect on the production of skin lesion by the virus except tetraethylammonium bromide had slightly inhibitory effect.

It has been previously reported that a filterable microorganism belonging to the genus Leptospira has been recovered from the blood or organs of human beings suffering from the disease known as yellow fever in Guayaquil, and that the organism, which has been termed Leptospira icteroides, induces in certain experimental animals the characteristic symptoms and lesions observed in the patients from whom it was isolated. It has also been previously shown that the serum from patients recovering from an attack of yellow fever in Guayaquil had the power to agglutinate and dissolve the organism when introduced into the peritoneal cavity of a normal guinea pig (Pfeiffer phenomenon). Moreover, the guinea pigs which had once been inoculated with the blood of yellow fever patients without succumbing to the infection, notwithstanding the fact that they had shown a definite febrile reaction after 4 to 5 days, were found to be refractory to a subsequent inoculation of a culture of Leptospira icteroides All these observations pointed to the possible relation of this organism to the disease known as yellow fever in Guayaquil. The demonstration of the filterability of the organism and the transmission of the infection with the same organism by Stegomyia calopus have further strengthened the probable etiological significance of the organism in yellow fever. It was by no means a simple problem to determine the relation existing between Leptospira icteroides and Leptospira icterohæmorrhagiæ. An experiment reported in a previous paper seemed to justify the view that the two leptospiras are closely related but not identical, yet it was necessary to exhaust various other modes of differentiation before the distinction between them was firmly established. The present paper continues this phase of the inquiry in further detail. There have been taken up here the phenomena of agglutination, the reaction of Pfeiffer, complement fixation, the protective properties of various monovalent and polyvalent immune sera, and active immunity. As the result of experiments in connection with these immunity phenomena the following data are presented. Monovalent immune sera prepared by several successive injections in an animal naturally refractory to Leptospira icteroides possess the power to agglutinate in vitro not only the homologous strains, but also all other strains of icteroides tested. On the other hand, a slight effect, or none at all, has been observed when these immune sera have been mixed in vitro with various strains of Leptospira icterohæmorrhagiæ. A similar relation exists between the monovalent anti-icterohæmorrhagiæ sera and the various strains of Leptospira icteroides; that is, there is a slight agglutinating effect in some instances upon the icteroides strains, but it is never so strong as that occurring in tests against the icterohæhagiæ strains. The Pfeiffer reaction gave a sharper differentiation between the two groups, for in most instances the phenomenon was specific for the group. There were occasional doubtful reactions, but not enough to warrant a confusion of the two groups. Polyvalent immune sera, one specific for icteroides, and the other for icterohæmorrhagiæ, showed a high titer of neutralizing power for the cultures of the homologous groups. It was found, however, that the action of the sera is by no means absolutely specific, because the injection of a sufficient amount of the anti-icteroides serum apparently prevented a fatal outcome in a guinea pig inoculated with multiple minimum lethal doses of a culture of Leptospira icterohæmorrhagiæ, and vice versa. The specificity of the serum was demonstrated only when it was used in smaller quantities. More or less specificity was shown by the complement fixation reaction, but it was not absolute. Weak fixation occurred when the anti-icteroides serum was mixed with one or the other of the icterohæmorrhagiæ strains and vice versa, and strong fixation occurred only when the antiserum was mixed with one of the icteroides strains. The question naturally arises whether or not this apparent specificity is due to the homology of the serum and not altogether to a difference in genus of the strains. In other words, it is justifiable to question whether all these variations in the degree of intensity of the reaction are not due to strain variations of the same genus. This question is not finally settled by the present investigation, in which only four icteroides and nine icterohæmorrhagiæ strains have been carefully studied. Nevertheless, on the basis of the findings with these thirteen strains, it seems probable that Leptospira icteroides and Leptospira icterohæmorrhagiæ are closely allied but are nevertheless distinct in their immunological reactions. Perhaps the difference between the two may amount to that between subspecies or races. It has been pointed out earlier that the pathogenicity of the two is also distinct, inasmuch as icteroides produces chiefly icterus and nephritis and icterohæmorrhagiæ hemorrhage and nephritis, the icterus being less and the hemorrhage more prominent in the evolution of the latter infection. In the study of active immunity—exclusive of vaccination—difficulty has been experienced in the evaluation of the results, owing to the existence of natural resistance to infection among guinea pigs. A guinea pig may recover from the inoculation of Leptospira icteroides and then resist a subsequent inoculation with a virulent strain of Leptospira icterohæmorrhagiæ, a condition simulating that brought about by the identity of the two organisms. However, the refractoriness of such an animal to icterohæmorrhagiæ may be due to its natural immunity to it. In the present study, therefore, only those guinea pigs were selected which had reacted typically—though in mild degree —to the icteroides infection, in order to determine whether they were subsequently immune to the inoculation of icterohæmorrhagiæ. Indeed, by this mode of experimentation it was found that the guinea pigs which had once passed through an attack of the icteroides infection were absolutely immune to a second infection with the same organism but reacted severely and sometimes fatally to a later inoculation of icterohæmorrhagiæ. Although there were a number of instances in which a previous infection with icteroides did not confer any perceptible immunity upon the guinea pigs against icterohæmorrhagiæ, another group of guinea pigs showed a considerable resistance to the icterohæmorrhagiæ infection as compared with those which had never been inoculated with icteroides. There is not much doubt, therefore, that an icteroides attack brings about, in some instances at least, a certain degree of resistance to the icterohæmorrhagiæ infection. Hence the study of the phenomena of active immunity strongly indicates that icteroides is closely related immunologically to icterohæmorrhagiæ.

SummaryChicks reared for 4 weeks on a modified non-fat milk diet deficient in copper developed mild anemia, leg weakness, bone deformities and a high incidence of subcutaneous hemorrhage. Mortality amounted to 23% and most deaths resulted from internal hemorrhage associated with rupture of major vessels. Histologic studies suggest a derangement of connective tissue metabolism with the major defect in elastic tissue.

It is not an infrequent experience to see a subcutaneous hemorrhage in the eye-lid or conjunctiva localized not always ipsilaterally but sometimes contralaterally after an Oto-Rhino-Laryngological operation, especially after a sinus operation.In order to eludidate the cause of the hemorrhage, the author performed the following experimental study on the rat: croton oil was injected into the tissue of the wall of the paranasal sinus or into the buccal mucosa through the lip. Ipsi- or contralateraly located palpebral hemorrhage was obeerved to occur following the injection.Histological study of the palpebral tissue revealed that the lesion was mainly due to the vascular disturbance with edema, vaso-dilatation, stagnation of blood cells and hemorrhage, as well as localized necrosis in severly damaged areas.Lesions were also found in the lungs, liver, kidneys and other organs. Suzuki. Iida and Fukazawa described similar lesions due to vascular disturbance in those organs of the pig produced as a manifestation of the Reilly's phenomenon.In the author's experiment, intensity of the palpebral hemorrhage and of the lesions in those organs pararelled with each other.These facts has induced the author to interprete the hemorrgagic lesion in the eye-lid as a manifestation of the Reilly's phenomenon.