Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's "Animal Rule." However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 10(4) spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans.

Edema of the limbs is a common reason for medical consultation, for which the lymphoscintigraphy is considered to be a reliable method for its differential diagnosis.To evaluate the usefulness of radionuclide studies in the differential diagnosis of edema, and the diagnostic yield of different scintigraphic patterns.A total of 61 patients, mean age 43 years, referred to our Department in the last three years for suspected lymphoedema, were considered. One patient was discarded due to lack of diagnosis, 56 had lower limb edema and 4 upper limb edema. After intradermal injection of two doses of (99m)Tc-nanocolloid, scintigraphic scans were made at 30 and 120minutes. The final diagnosis was based on imaging tests, clinical course, and response to treatment. We calculated the parameters of the diagnostic yield of four different scintigraphic patterns (presence of dermal backflow, asymmetry-alteration in inguinal/axillary nodes, presence of collateral pathways, and visualization of intermediate lymph nodes), considering them individually and jointly.The best diagnostic yield was achieved by considering dermal backflow and asymmetry in inguinal/axillary nodes (accuracy 88.9%, specificity 96.4%, PPV 95.5%). Evaluation of intermediate lymph nodes and presence of collateral pathways contributed little to the diagnostic yield, showing poor sensitivity and high false positive rates.The lymphoscintigraphy had high diagnostic yield, allowing early treatment of lymphœdema. The dermal backflow and asymmetry in inguinal/axillary nodes had the greatest diagnostic accuracy. Evaluation of intermediate lymph nodes and visualization of collateral pathways contributed little to improving the diagnosis.

The efficient transport of blood and lymph relies on competent intraluminal valves that ensure unidirectional fluid flow through the vessels. In the lymphatic vessels, lack of luminal valves causes reflux of lymph and can lead to lymphedema, while dysfunction of venous valves is associated with venous hypertension, varicose veins, and thrombosis that can lead to edema and ulcerations. Despite their clinical importance, the mechanisms that regulate valve formation are poorly understood and have only recently begun to be characterized. Here, we discuss new findings regarding the development of venous and lymphatic valves that indicate the involvement of common molecular mechanisms in regulating valve formation in different vascular beds.

In healthy people, no retrograde lymph flow occurs because of valves in collecting lymph vessels. However, in secondary lymphedema after lymph node dissection, lymph retention and lymphatic hypertension occurs and valvular dysfunction induces retrograde lymph flow. In this case reported, we focused on retrograde lymph flow and performed retrograde lymphatico-venous anastomosis (LVA) simultaneously with antegrade LVA. A 67-year-old Japanese woman had worsening edema in her right thigh and hip area for 3 years. She had previously undergone extended hysterectomy with lymph node dissection for endometrial cancer 8 years before. Indocyanine green test showed antegrade and retrograde lymph flow. Four LVAs were made in the right medial thigh and right lower abdominal area under local anesthesia. Lymphedema showed rapid improvement within 12 months and compression therapy was not required at 24 months after LVA. Retrograde LVA has a possibility of a more efficacy for secondary lymphedema.

We report a 3-year-old girl with Kawasaki disease who presented with retropharyngeal edema and shock syndrome. This is the first reported case in Taiwan. The patient initially presented with fever, cough, and pyuria followed by rapidly progressive enlarged bilateral cervical lymphadenopathy. On the third day of the fever, computed tomography for airway compression sign found widening of the retropharyngeal space mimicking a retropharyngeal abscess. Later, an endotracheal tube was inserted for respiratory distress. A skin rash over her trunk was also noted. On the fifth day of the fever, the clinical course progressed to hypotension and shock syndrome. Because of more swelling of bilateral neck lymph nodes, computed tomography was arranged again and revealed partial resolution of the edematous changes in the retropharyngeal space. Edema of the hands and feet, bilateral bulbar conjunctivitis, and fissured lips were subsequently found. The diagnosis of Kawasaki disease was confirmed on the eighth day of fever. There was no evidence of bacterial infection. She was administered intravenous immunoglobulin (2 mg/kg) and high dose aspirin (100 mg/kg/day). One day later, the fever subsided, and her blood pressure gradually became stable. Heart echocardiography on the Day 13 revealed dilated left coronary artery and mitral regurgitation. Follow-up echocardiography six months later showed normal coronary arteries. To date, the patient has not experienced any complications. This case illustrates that retropharyngeal edema and shock syndrome can be present in the same clinical course of Kawasaki disease. Clinicians and those who work in intensive care units should be aware of unusual presentations of Kawasaki disease to decrease rates of cardiovascular complications.

OPINION STATEMENT: The past decade has produced an explosion of insights into lymphatic vascular development and structural biology and, in parallel, into the function of the lymphatics in health and in disease. In lymphedema, there is a spectrum that extends from primary (heritable) to acquired causes of disease. The diagnosis of lymphatic edema implicates a very specific treatment approach that is predicated upon the favorable impact of physiotherapy upon lymph flow and protein clearance from the edematous zones of the body. The recognition of the unique biology that accompanies lymphatic causes of edema has stimulated new research directions that are likely to translate into exciting new pharmacologic and molecular approaches to diagnosis and treatment.

I.V. fluid therapy does not result in the extracellular volume distribution expected from Starling's original model of semi-permeable capillaries subject to hydrostatic and oncotic pressure gradients within the extracellular fluid. Fluid therapy to support the circulation relies on applying a physiological paradigm that better explains clinical and research observations. The revised Starling equation based on recent research considers the contributions of the endothelial glycocalyx layer (EGL), the endothelial basement membrane, and the extracellular matrix. The characteristics of capillaries in various tissues are reviewed and some clinical corollaries considered. The oncotic pressure difference across the EGL opposes, but does not reverse, the filtration rate (the 'no absorption' rule) and is an important feature of the revised paradigm and highlights the limitations of attempting to prevent or treat oedema by transfusing colloids. Filtered fluid returns to the circulation as lymph. The EGL excludes larger molecules and occupies a substantial volume of the intravascular space and therefore requires a new interpretation of dilution studies of blood volume and the speculation that protection or restoration of the EGL might be an important therapeutic goal. An explanation for the phenomenon of context sensitivity of fluid volume kinetics is offered, and the proposal that crystalloid resuscitation from low capillary pressures is rational. Any potential advantage of plasma or plasma substitutes over crystalloids for volume expansion only manifests itself at higher capillary pressures.

Postoperative lymphedema after breast cancer surgery is a challenging problem. Recently, a novel microvascular lymph node transfer technique provided a fresh hope for patients with lymphedema. We aimed to combine this new method with the standard breast reconstruction.During 2008-2010, we performed free lower abdominal flap breast reconstruction in 87 patients. For all patients with lymphedema symptoms (n = 9), we used a modified lower abdominal reconstruction flap containing lymph nodes and lymphatic vessels surrounding the superficial circumflex vessel pedicle. Operation time, donor site morbidity, and postoperative recovery between the 2 groups (lymphedema breast reconstruction and breast reconstruction) were compared. The effect on the postoperative lymphatic vessel function was examined.The average operation time was 426 minutes in the lymphedema breast reconstruction group and 391 minutes in the breast reconstruction group. The postoperative abdominal seroma formation was increased in patients with lymphedema. Postoperative lymphoscintigraphy demonstrated at least some improvement in lymphatic vessel function in 5 of 6 patients with lymphedema. The upper limb perimeter decreased in 7 of 9 patients. Physiotherapy and compression was no longer needed in 3 of 9 patients. Importantly, we found that human lymph nodes express high levels of endogenous lymphatic vessel growth factors. Transfer of the lymph nodes and the resulting endogenous growth factor expression may thereby induce the regrowth of lymphatic network in the axilla. No edema problems were detected in the lymph node donor area.Simultaneous breast and lymphatic reconstruction is an ideal option for patients who suffer from lymphedema after mastectomy and axillary dissection.

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The diagnostic criteria are fulfilled with fever of unknown origin and 4 of the following 5 criteria: bilateral conjunctival injection, cervical lymphadenopathy, polymorphous rash, oral mucous membrane changes (injected lips, strawberry tongue) and peripheral extremity changes (erythema, edema, desquamation). If less than 4 criteria are found incomplete KD can be diagnosed. The therapy is 2 g/kg body weight single dose intravenous immunoglobulin and acetylsalicylic acid (ASS). In the long-term follow-up the main focus is on the coronary arteries because coronary changes play a key role in the intensity of long-term management. There is some evidence that KD is a risk factor for cardiovascular diseases in adults.

Advances in cancer therapy have increased the importance of improvement of quality of life after cancer survival. Cancer-related lymphedema or secondary lymphedema that occurs after lymph node dissection in resection of tumors of abdominal visceral organs can impair quality of life. However, standard curative treatment for secondary lymphedema has not been established. This may be due to the lack of a method for early diagnosis of lymphedema, and because of selection of conservative treatment such as compression therapy to delay edema progression in many cases. To develop a curative approach, we have performed definite diagnosis of early-stage lymphedema using magnetic resonance imaging and an indocyanine green fluorescent lymphography, followed by surgical treatment with lymphatic-venous anastomosis using supermicrosurgery. Herein, we report the first case of secondary lymphedema in which we performed early diagnosis and surgery using these techniques and achieved an almost complete cure of lymphedema. We suggest that early diagnostic imaging and early microsurgery is the key of lymphedema treatment.