THE EFFECT OF MULTIPLE EMBOLI OF THE CAPILLARIES AND ARTERIOLES OF ONE LUNG

1. Injection of a suspension of potato starch cells into the left branch of the pulmonary artery, in quantity sufficient ordinarily to give rise to markedly accelerated respirations, resulted in no change in respiratory rate. 2. A method for injecting substances into the pulmonary artery or its branches without interfering with the blood flow to the lungs has been described. 3. Injection of similar material into one lung when the other is excluded from the circulation either by ligation or by temporary clamping does give rise to rapid and shallow breathing (from a rate of 10 to 15 per minute to one of 60 or over) identical in character to that brought about by introducing emboli into both lungs. 4. A method for clamping and releasing the pulmonary artery or its branches in a dog breathing normally with closed thorax has been devised. This is described in detail in another paper. 5. After rapid breathing has been initiated by the effect of emboli lodged in the arterioles and capillaries of the right lung, reestablishing the circulation in the other lung by releasing the clamp on its artery may or may not restore the respiratory rate to its original, normal level. 6. This discrepancy in results has not been correlated with any difference in oxygen saturation of the arterial blood, or in carbon dioxide tension or pH of its plasma. 7. It is, however, believed to be related to the gross and microscopic anatomy of the lung of which the artery has been temporarily clamped. Photomicrographs are published, showing in one dog (No. 3), in which the respiratory rate returned to normal, a normal histological picture of the left lung, and in another dog (No. 4), in which the rate remained rapid after release of the clamp, a picture characterized by congestion and dilatation of arterioles and capillaries. 8. The fact that accelerated respirations result from emboli in the pulmonary capillaries and arterioles only after a certain quantity of material has been introduced, and the fact that emboli in one lung do not occasion accelerated respirations unless the circulation through the other lung is occluded or abnormal, leads us to the conclusion that the phenomenon is not an irritative stimulus due to foreign bodies, but is in some manner related to (a) diminution of the pulmonary vascular bed, (b) resistance to the blood flow through the lungs or (c) congestion or dilatation of the arterioles and capillaries of the lungs.     

THE INTRARENAL PRESSURE DURING EXPERIMENTAL RENAL HYPERTENSION

The intrarenal interstitial pressure was measured during the course of experimental renal hypertension in dogs. In perinephritic hypertension, produced by wrapping the kidney in a cellophane bag, the intrarenal pressure rose slowly from the normal value of 25 mm. Hg to a final level of about 60 mm. Hg. Strong pressure pulsations were observed in the renal parenchyma during this type of hypertension. In the hypertension following partial occlusion of the renal artery, the intrarenal pressure remained approximately normal, except in malignant hypertension when it tended to decline to about 9 mm. Hg. The hypertension of perinephritis is interpreted as a consequence of renal ischemia, the high intrarenal pressure, produced by the constricting fibrotic hull, acting to reduce the effective perfusion pressure of the kidney. The two experimental hypertensions herein examined are considered as examples of influent resistance hypertensions and effluent resistance hypertensions, the former being due to renal arterial or arteriolar resistance and the latter due to renal venous resistance, specifically at the arcuate-interlobar junction. The application of this concept to renal hypertensive disease in man is discussed.     

LC3-associated phagocytosis in bone marrow macrophages suppresses acute myeloid leukemia progression through STING activation

The bone marrow (BM) microenvironment regulates acute myeloid leukemia (AML) initiation, proliferation, and chemotherapy resistance. Following cancer cell death, a growing body of evidence suggests an important role for remaining apoptotic debris in regulating the immunologic response to and growth of solid tumors. Here, we investigated the role of macrophage LC3–associated phagocytosis (LAP) within the BM microenvironment of AML. Depletion of BM macrophages (BMMs) increased AML growth in vivo. We show that LAP is the predominate method of BMM phagocytosis of dead and dying cells in the AML microenvironment. Targeted inhibition of LAP led to the accumulation of apoptotic cells (ACs) and apoptotic bodies (ABs), resulting in accelerated leukemia growth. Mechanistically, LAP of AML-derived ABs by BMMs resulted in stimulator of IFN genes (STING) pathway activation. We found that AML-derived mitochondrial damage–associated molecular patterns were processed by BMMs via LAP. Moreover, depletion of mitochondrial DNA (mtDNA) in AML-derived ABs showed that it was this mtDNA that was responsible for the induction of STING signaling in BMMs. Phenotypically, we found that STING activation suppressed AML growth through a mechanism related to increased phagocytosis. In summary, we report that macrophage LAP of apoptotic debris in the AML BM microenvironment suppressed tumor growth.     

Carotid artery stents for blunt cerebrovascular injury: risks exceed benefits

BACKGROUND: Carotid stenting has been advocated in patients with grade III blunt carotid artery injuries (hereafter referred to as "blunt CAIs") because of the persistence of the pseudoaneurysm and concern for subsequent embolization or rupture. HYPOTHESIS: Carotid stenting is safe and effective for blunt CAIs. DESIGN: Analysis of a prospective database of all patients with blunt CAIs. SETTING: A state-designated, level I, urban trauma center.Patients and METHODS: In January 1, 1996, we initiated comprehensive screening for blunt CAIs with angiography based on injury patterns. Patients without contraindications receive anticoagulation therapy immediately for documented lesions. Patients with persistent pseudoaneurysms on a second angiography at 7 to 10 days after injury are candidates for stent placement. RESULTS: During the study period (January 1, 1996, to May 1, 2004), 46 patients sustained blunt carotid pseudoaneurysms; 23 (50%) underwent carotid stent placement. There were 4 complications in patients undergoing carotid stent placement: 3 strokes and 1 subclavian dissection. Follow-up angiography was performed in 38 patients (18 patients with stents who received antithrombotic agents, 20 patients who received antithrombotic agents alone); 8 patients had poststent carotid occlusion despite having received concurrent anticoagulation therapy. Carotid occlusion rates were significantly different (45% in patients with stents vs 5% in those who received antithrombotic agents alone). In the patients not undergoing stent placement, the only complication was a middle cerebral artery stroke in a patient not treated with antithrombotic therapy. CONCLUSIONS: Patients who have carotid stents placed for blunt carotid pseudoaneurysms have a 21% complication rate and a documented occlusion rate of 45%. In contrast, patients treated with antithrombotic agents alone had an occlusion rate of 5%; no asymptomatic patient treated with antithrombotic agents for their injury had a stroke. Antithrombotic therapy remains the recommended therapy for blunt CAIs, but the role of intraluminal stents remains to be defined.     

Perigraft seroma: clinical, histologic, and serologic correlates

A 14 year retrospective study of perigraft seroma, defined as an enlarging sterile fluid collection at the site of a prosthetic graft, revealed well-documented cases in 5 of 118 extraanatomical bypasses (4.2 percent), 3 of 248 aortic reconstructive procedures (1.2 percent), and 1 of 395 femoropopliteal bypasses (0.3 percent). These nine cases involved four polytetrafluoroethylene and five Dacron grafts. There were five graft thromboses, one instance of limb loss, two graft infections, two deaths, and 13 separate surgical procedures related to the perigraft seroma. Histologic studies revealed a fibrous pseudomembrane lining the perigraft seroma wall and immature fibroblasts lining the graft. Sera from three patients with perigraft seroma, five patients with well-incorporated prosthetic grafts, and three healthy volunteer subjects were tested for in vitro evidence of fibroblast inhibition against fibroblast tissue cultures derived from the pseudomembrane of a perigraft seroma. Control fetal calf serum, sera from all three healthy subjects, and sera from all five patients with well-incorporated grafts allowed fibroblast proliferation. In contrast, sera from all three patients with perigraft seroma inhibited fibroblast growth. Furthermore, sera collected 1, 2, and 3 months after graft removal from one patient and serum collected 3 months after spontaneous resolution of a perigraft seroma from another patient failed to inhibit fibroblasts. We have concluded that patients with perigraft seroma have a high rate of graft and limb loss and require multiple reoperations. The pathogenesis of perigraft seroma appears to involve a humoral fibroblast inhibitor which prevents maturation and proliferation of perigraft fibroblasts, leading to poor graft incorporation. The decrease of inhibition below detectable levels after graft removal or spontaneous resolution of the perigraft seroma suggests that the graft may induce host production of the inhibitor. Effective therapy of perigraft seroma may include fibroblast modulation, removal of the inciting graft, or both.     

A quantitative ultrastructural study of collagen fibril formation in the healing extensor digitorum longus tendon of the rat

A study was made of collagen fibril populations in healing tendon using a window lesion in rat extensor tendon. Two environments were thus created. One (the lesion area) where stress levels were reduced; the other (the non-lesion area) where stress levels were increased. In both areas a population of small diameter (less than 50nm) collagen fibrils were synthesized. Lesion area fibrils increased their diameter only slowly. Non-lesion area fibrils added to a population which increased its diameter distribution comparatively rapidly. It is suggested that in the lesion area fibrils were synthesized in response to tissue damage and low levels of stress. These may be of type III collagen. In the non-lesion area fibrils were synthesized in response to raised levels of stress. These may be of type I collagen. Implications of these events, especially as they might relate to gap formation in flexor tendon surgery are discussed.     

Acute and chronic open conversion after endovascular aortic aneurysm repair: a 14-year review

OBJECTIVE: This study reviewed outcomes of patients requiring surgical conversion after endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Records for all patients undergoing open conversion after endovascular AAA repair were reviewed. RESULTS: From 1993 to 2006, 574 patients underwent endovascular repair for AAA. Seventeen patients, including three patients who underwent prior endovascular repair at other centers, required surgical conversion with complete (n = 9) or partial graft removal (n = 8). Five patients required immediate conversion (acute), and 12 underwent delayed conversion 4 to 72 months after endovascular repair. Indications for acute conversion were large type I endoleak (n = 3, 60%), including one patient with graft migration, and retroperitoneal bleeding (n = 2, 40%). Indications for chronic conversion were endoleak with increasing aneurysm size (n = 9, 75%), stent fracture without endoleak (n = 1, 8%), delayed retroperitoneal bleeding (n = 1, 8%), and infection (n = 1, 8%). Suprarenal aortic cross-clamping was required in two patients (12%), and endograft components were retained in eight (47%). An aortic occlusion balloon placed through the body of the existing endograft facilitated proximal control in three patients. There were two perioperative deaths in the acute conversion group (2/5; 40%) and none in the delayed conversion group (P = .04). Five-year actuarial survival was 71.9%. Mean follow-up was 41.6 +/- 32.2 months. Retained endovascular components in patients with partial graft removal remained stable during follow-up. CONCLUSIONS: Surgical conversion after endovascular AAA repair can be performed without suprarenal clamping in most patients. Endovascular aortic control with a balloon avoids suprarenal exposure. Partial endograft removal in selected patients facilitates open conversion and appears durable. Acute conversion is associated with increased mortality.     

A high-fidelity,virtual-reality,transurethral resection of bladder tumor simulator: Validation as a tool for training

IntroductionSimulation-based training is used to help trainees learn surgical procedures in a safe environment. The objective of our study was to test the face, content, and construct validity of the transurethral resection of bladder tumor (TURBT) module built on the Simbionix TURP Mentor simulator.MethodsParticipants performed five standardized cases on the simulator. Domains of the simulator were evaluated on a five-point Likert scale to establish face and content validity. Construct validity was assessed through the simulator’s built-in scoring metrics, as well as video recordings of the simulator screen and an anonymized view of participants’ hands and feet, which were evaluated using an objective structured assessment of technical skills (OSATS) tool.ResultsTen experienced operators and 15 novices participated. Face validity was somewhat acceptable (mean realism 3.8/5±1.03 standard deviation [SD]; mean appearance 4.1/5±0.57), as was content validity, represented by simulation of key steps (mean 3.9±0.57). The simulator failed to achieve construct validity. There was no difference in mean simulator scores or OSATS scoring between experienced operators and novices. Novices significantly improved their mean simulator scores (305.9 vs. 332.4, p=0.006) and OSATS scoring (15.8 vs. 18.1, p=0.001), while 87% felt their confidence to perform TURBT improved. Overall, 92% of participants agreed that the simulator should be incorporated into residency training.ConclusionsOur study suggests a role for the TURBT module of the Simbionix TURP Mentor simulator as an introduction to TURBT for urology trainees. Strong support was found from both experienced operators and novices for its formal inclusion in resident education.     

Neuroendocrine tumors of the rectum: a 10-year review of management

Neuroendocrine tumors of the rectum constitute approximately 19 per cent of gastrointestinal neuroendocrine tumors (NETs). The histologic characteristics of the tumor seem to be an indicative prognostic factor. Optimal treatment of NETS of the rectum has been widely debated, but more recent studies suggest that treatment depends upon the size. The medical records of 37 patients with NETS of the rectum were retrospectively reviewed. We reviewed their presentation, surgical treatment, pathology, and outcome. All pathological specimens were reviewed. Neuroendocrine tumors of the rectum were classified as either well-differentiated tumors, well-differentiated neuroendocrine carcinoma, or poorly differentiated neuroendocrine carcinoma. Evaluating tumor size, we found 35/37 patients had tumors less than 1 cm, 1 patient had a tumor between 1 and 2 cm, and one had a tumor greater than 2 cm. Pathologic evaluation of the tumors revealed that 35 of the tumors invaded the submucosa only, one invaded the muscularis propria, and one invaded the perirectal adipose tissue. The histopathologic features of the tumors revealed that 34 of the tumors were well-differentiated NETS with benign features, one tumor had invaded the submucosa, with angioinvasion, and two tumors were neuroendocrine carcinoma. Thirty-five patients underwent local excision. Eleven had reexcisions for positive margins. Two patients had local excision for recurrence, and one patient underwent low anterior resection (4 cm). Twelve patients had negative margins, 25 had positive margins. Eleven patients underwent reexcision. Six had no evidence of residual disease, and five had persistent positive margins and were offered no further treatment. Nineteen patients had positive margins and did not have reexcision. They all had tumors < 1 cm. Despite half of the lesions being resected with final pathologic positive margins, we have seen no significant influence on recurrence or overall survival. This raises the question of margin clearance in early lesions.