Alveolar epithelial damage. A critical difference between high pressure and oleic acid-induced low pressure pulmonary edema.

The present study was designed to compare high pressure pulmonary edema (HPPE) and oleic acid-induced low pressure pulmonary edema (OAPE) in dogs when similar amounts of extra vascular water were present in the lung. The high pressure edema was produced by intravenous fluid overload and by inflating an aortic balloon catheter (n = 6). The low pressure edema was produced by the injecting 0.08 mg/kg oleic acid suspended in 5 ml saline (n = 6). Comparison of the difference between initial control measurements and final measurements in the edematous states showed that the animals with OAPE had a greater fall in percent oxygen saturation and a greater increase in shunt fractions. The light microscopic studies showed that OAPE was associated with greater amounts of alveolar flooding than HPPE where the edema fluid was located to a greater extent in the peribronchial interstitial space. The electron microscopy studies showed that the alveolar flooding in OAPE was associated with epithelial disruption, and tracer studies carried out in rabbits showed that dextran (150,000 mol wt) could pass from blood to airspace and that dextran (40,000 mol wt) could pass from air-space to blood in OAPE. We conclude that epithelial disruption is responsible for the excessive alveolar flooding in OAPE and that this results in a greater impairment in gas exchange.

Comparison of cellular immunotherapies and anti-CD3 in the treatment of MCA-38-LD experimental hepatic metastases in C57BL/6 mice.

An experimental model of hepatic metastases in C57BL/6 mice was used to compare the antitumor effects of lymphokine-activated killer (LAK) cells, anti-CD3-activated T-cells (ATC), and anti-CD3 alone. Liver metastases were produced by in vivo passage of MCA-38-LD adenocarcinoma via the ileocolic vein. LAK cells and ATC were generated by 3-day in vitro incubation of spleen cells in interleukin 2 and anti-CD3, respectively. Percentage of tumor volume in livers was determined with a morphometric technique. With less than therapeutic LAK cell doses (0.5-1.0 x 10(7) cells), no effect was seen in mean (+SE, -SE) percentage of tumor volume of control [23.3 (29.3, 18.5)] compared to LAK cell-treated [21.6 (29.3, 15.9)] animals. The same number of ATC significantly reduced the mean percentage of tumor volume [2.7 (4.7, 1.4)] (P less than 0.005). High dose interleukin 2 also significantly decreased tumor volume. More strikingly, a single dose of anti-CD3 alone had a beneficial effect on mean percentage of tumor volume when given i.p. [1.0 (1.9, 0.4)] or i.v. [1.2 (1.7, 0.7)] (P less than 0.0003). A total of 33% of anti-CD3-treated mice had no detectable liver metastases. In 51Cr release assays, the cytotoxicity of ATC was shown to be partially mediated by nylon wool-adherent accessory cells. The effectiveness of anti-CD3 in this immunotherapy model suggests that a similar approach may be taken to immunotherapy of human malignancies, without the requirements for in vitro-generated killer cells or exogenously administered interleukin 2.

The effect of a venous filter on the embolic load during medullary canal pressurization: a canine study.

BACKGROUND: Acute intramedullary stabilization of femoral shaft fractures in multiply injured patients is controversial. Intravasation of medullary fat during canal pressurization has been suspected to trigger adult respiratory distress syndrome. The goal of the present study was to evaluate the effect, on the lungs, of a filter placed into the ipsilateral common iliac vein during medullary canal pressurization in a canine model. METHODS: With use of an established model of fat embolization, twelve mongrel dogs were randomized into two groups. In six dogs, a special filter was inserted percutaneously into the left common iliac vein while the dogs were under general anesthesia. In all dogs, the left femur and tibia were then pressurized by injection of bone cement and insertion of intramedullary rods. Hemodynamic measurements and echocardiographic images were recorded throughout the experiment. After one hour, the animals were killed and the lungs were harvested for histomorphometric analysis. RESULTS: Without the filter, the mean pulmonary artery pressure increased by 11.8 +/- 2.1 mm Hg (p < 0.001). With the filter, the mean pulmonary artery pressure increased by only 2.2 +/- 0.8 mm Hg (p < 0.02). Without the filter, there was a significant increase in the index of pulmonary vascular resistance as compared with the baseline value (p < 0.05). With the filter, there was no such increase. Histomorphometric analysis demonstrated that the presence of the filter reduced the absolute area of embolization and the volume percentages of lung and pulmonary vasculature embolized. CONCLUSIONS: In this canine experiment, temporary placement of a venous filter prior to medullary canal pressurization reduced the embolic load and minimized its hemodynamic effects.

Morphologic diagnosis of idiopathic pulmonary alveolar lipoproteinosis-revisited.

The usefulness of transbronchial biopsy in diagnosing idiopathic pulmonary alveolar lipoproteinosis (PAL) is not emphasized in the literature. Therefore, we decided to reassess our approach to the morphologic diagnosis of this disorder in 14 patients diagnosed over the past 13 years in two major teaching hospitals in Toronto. The morphologic diagnosis of idiopathic PAL was established by means of open lung biopsy in 11 patients; the use of transbronchial biopsy was not considered in eight of them. Transbronchial biopsy was performed in six patients, and the diagnosis of idiopathic PAL was reliably established in five cases. We conclude that transbronchial biopsy may be a worthwhile preliminary procedure to open lung biopsy in patients with suspected idiopathic PAL, and it can reliably establish the diagnosis in such cases.

Characterization of a highly metastatic, orthotopic lung cancer model in the nude rat.

The prevailing subcutaneous nude rodent tumor xenograft models used for biological and preclinical studies do not optimally reflect some important biological properties of cancer, especially invasion and metastasis. Orthotopic models have been developed to address this need. However, for lung cancer none of the available models are optimal, in that none originate from an orthotopic (bronchial) primary site and exhibit extensive extrathoracic metastasis. Our goal was to develop a consistent rodent model of non-small cell lung cancer with both of these properties. Groups of male Rowett nude rats were given 500 rads of gamma radiation and then endobronchially implanted in the right caudal lobe airway with 50 mg of small NCI-H460 tumor fragments taken from an orthotopic donor tumor. They were then sacrificed at selected post-implantation times and evaluated grossly and histologically for animal weight, primary tumor take and size, and metastatic tumor incidence at multiple sites. At a late time point (32-35 days), consistency of primary tumor size and metastasis was estimated by comparing results from four groups of rats implanted on different occasions. The results showed that the primary tumors grew steadily, reaching four grams by days 32-35. Rats gained weight until days 14 to 21, but then began to show cachexia. High metastatic rates (>60%) were seen for mediastinal lymph nodes (by 21 days), and kidney, bone and brain (by 28 days). Mean primary tumor size and the incidences of both regional and systemic metastasis were consistent at 32-35 days in four different groups of six animals. In conclusion, this orthotopic lung cancer model is highly metastatic and consistent in terms of both primary tumor growth and metastatic behavior. It is the only available rodent model of human lung cancer emanating from an endobronchial site and metastasizing to multiple extrapulmonary sites, and should be very useful for both biological and preclinical studies of lung cancer, particularly where studies of antimetastatic activity are of interest, and/or where survival studies are desired.

Evidence that cold preservation-induced microcirculatory injury in liver allografts is not mediated by oxygen-free radicals or cell swelling in the rat.

The critical injury of cold preservation is to the hepatic microcirculation. Oxygen free radical injury and cell swelling have been proposed to be causes of allograft failure, and new solutions such as Marshall's isotonic citrate and University of Wisconsin (UW) solutions were designed to prevent cell swelling and free radical injury. Experiments were done to determine whether Marshall's solution and UW solution protect the microcirculation, and whether they do so by preventing cell swelling or free radical-induced injury. To determine if the new solutions reduce sinusoidal lining cell injury, rat livers were examined after preservation at 4 degrees C in NaCl 0.9% and CaCl2 2 mM for 4 hr and 8 hr, in Collins' solution for 8 hr, and in both UW and isotonic citrate solutions for 8 hr and 16 hr. Next, the role of cell swelling in preservation injury was studied by storing livers in hypotonic solutions that accelerate liver weight gain, and in a choline chloride-based preservation solution. Finally, to evaluate the role of active oxygen species, SOD, catalase, and allopurinol were added to preservation solutions. The effect of allopurinol alone was also studied. In a related study, sucrose was substituted for the free radical scavenger, mannitol, in isotonic citrate solution. All livers were studied by light microscopy after perfusion-fixation. Storage in UW and isotonic citrate solutions resulted in clear improvement in the morphology of the sinusoidal lining. Increasing the rate of liver weight gain by the use of hypotonic solutions did not accelerate the endothelial injury. Choline chloride-based solution prevented weight gain during preservation, but unlike UW or isocitrate solutions it did not retard the microcirculatory injury. After preservation in the presence of SOD and catalase, or allopurinol, no improvement in the defined morphological features of the endothelial injury was noted when compared with respective controls; nor was the benefit of isotonic citrate solution lessened by the removal of the free radical scavenger mannitol. We conclude that microvascular injury produced by cold injury is due neither to free radical-mediated injury nor to cell swelling. As both UW and isotonic citrate solutions provide significant protection to the microcirculation, they must do so by a yet-undetermined mechanism.

Prediction of the outcome of transplantation in man by platelet adherence in donor liver allografts. Evidence of the importance of prepreservation injury.

We examined platelet adhesion in thirty human donor livers to determine if the degree of platelet adhesion could predict outcome of transplantation. Wedge liver biopsies were taken at the start of the donor operation (biopsy 1) and 1 hr after reperfusion in the recipient (biopsy 2). Biopsies were stained with a monoclonal antibody against platelet glycoprotein Ib and graded for platelet adhesion. Hematoxylin and eosin-stained sections were examined for polymorphonuclear leukocyte adhesion and necrosis. Platelet adhesion was much more frequent and extensive than expected in biopsy 1. Nine of 30 biopsies showed moderate or high-grade platelet adhesion. Thus in this study endothelial cell damage was present in about one-third of donors before the donor operation. The injury was not detectable by routine microscopic or clinical examination or biochemical tests. The degree of platelet adhesion in biopsy 1 predicted development of PMN adhesion and necrosis in biopsy 2 and postoperative transaminase concentrations and prothrombin times in recipients. During preservation and implantation some livers converted from low to either moderate or high grades of platelet adhesion. The grade of platelet adhesion in biopsy 2 predicted postoperative outcome as measured by transaminase and PT levels. Patients whose platelet grade converted to a higher level during preservation and implantation did not do as well as patients who remained at a low adhesion grade. These findings strongly suggest that the degree of platelet adhesion is an important determinant in assessing outcome and may provide a means of measuring the status of liver allografts prior to transplantation.

A study of smoking, p53 tumor suppressor gene alterations and non-small cell lung cancer.

PURPOSE: The purpose of this study was to investigate the relationship between smoking and p53 tumor suppressor gene alterations, and their association with clinicopathologic features and prognosis in non-small cell lung cancer (NSCLC). METHODS: For 111 of 119 stage I-III NSCLC patients that had been followed prospectively, tumor p53 protein accumulation was measured immunohistochemically (IHC). Staining was evaluated as a score (p53IHCS) combining intensity and percent distribution. RESULTS: Forty-eight of 111 (43%) tumors had p53IHCS > 1. p53 IHC was associated with increasing tumor size (T) (p = 0.035), nodal status (N) (p = 0.091), stage (p = 0.054), and histology: squamous cell carcinoma (70%) and adenocarcinoma (27%) (p = 0.0002). In logistic regression analysis, p53 IHC was associated with squamous cell histology versus other histotypes [adjusted odds ratio (OR)5.90, 95% confidence interval (CI) 2.34-14.90]. p53 IHC was not associated with smoking variables. In multivariate proportional hazards analysis, p53IHCS and pack-years smoked (PY), both as continuous variables, were negative prognostic factors. The adjusted hazard ratios (HR) for the survival outcome recurrence for p53IHCS and PY were 1.20 (95% CI 1.02-1.40) and 1.03 (95% CI 1.01-1.04), and for death due to recurrent disease (DRD) were 1.35 (95% CI 1.11-1.64) and 1.03 (95% CI 1.01-1.04), respectively. Comparing the 75th percentile to the baseline 0, the adjusted HR for p53IHCS (5 vs. 0) was 4.5 and for PY (55 vs. 0) was 5.1 for the outcome DRD. Both variables demonstrated a dose-response relationship with survival. CONCLUSIONS: PY and p53IHCS are significant, independent and important predictors of recurrence and DRD in stage I-III NSCLC.

Deferoxamine induces hypotension in experimental gram-negative septicemia.

Multiple organ system failure may result from tissue damage caused by activated neutrophils or endotoxin. A significant part of this tissue damage is due to peroxidation induced by oxygen-free radicals and requires iron as a co-factor. Iron chelation has been shown to prevent tissue damage in some models. This experiment was carried out to determine whether iron chelation with deferoxamine (DFO) would prevent lung damage in a swine model of Gram-negative septicemia. Fifteen animals were randomized to control, Pseudomonas aeruginosa infusion at a rate of 2 x 10(7) colony forming units/20 kg/min (septic group), or Pseudomonas infusion combined with DFO pretreatment at a dose of 80 mg/kg/h (septic-treated group). Three of six septic-treated animals became severely hypotensive and died during the course of the experiment as opposed to none of six septic animals. Surviving septic-treated animals were significantly hypotensive (60 +/- 24 mmHg mean arterial pressure) compared to septic (122 +/- 9 mmHg) and control (109 +/- 8 mmHg) animals. DFO did not improve respiratory function (e.g., pO2) or morphology in septic animals. We conclude that iron-chelation therapy with DFO at the above dosage results in a significant deterioration in cardiovascular function in septic swine. Lung damage was not prevented.

The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation.

We have previously demonstrated that a low-potassium dextran solution provides superior and more reliable preservation of lungs for 12 hours than that provided by the commonly used Euro-Collins solution. This study was designed to examine the individual contributions of dextran 40 and a low (extracellular) potassium concentration to lung preservation. In a randomized, blinded study using an in vivo canine single-lung transplant model, lungs preserved with low-potassium dextran solution (K+, 4 mmol/L; dextran 40, 20 gm/L) were compared to lungs preserved with low-potassium, no-dextran solution (K+, 4 mmol/L) and high-potassium dextran solution (K+, 123 mmol/L; dextran 40, 20 gm/L). The lungs were assessed immediately and 3 days after transplantation. The low-potassium dextran solution provided excellent immediate pulmonary function with little variability (arterial oxygen tension, 519 +/- 12 mm Hg, measured on the transplanted lung alone, inspired oxygen fraction = 1.0, n = 6). Removing the dextran 40 from the flush solution (low-potassium group) led to a significant deterioration in pulmonary function (arterial oxygen tension, 243 +/- 78 mm Hg, n = 6, p less than 0.01). The high-potassium dextran solution provided extremely poor preservation (arterial oxygen tension, 176 +/- 79 mm Hg; n = 6; p less than 0.01). Two animals in this group died within 6 hours of operation. Viability of the transplanted bronchus was significantly improved with the two solutions containing dextran 40. These results indicate that dextran 40 and low potassium concentration both contribute significantly to the uniformly excellent 12-hour lung preservation seen with the low-potassium dextran solution.

Transplant immunosuppression increases and prolongs transgene expression following adenoviral-mediated transfection of rat lungs.

BACKGROUND: Gene therapy provides the potential to modify donor organs to better withstand transplantation, but this has yet to be realized. In vivo gene transfer using adenoviral vectors has had limited success because of host immune response that induces inflammation and limits the amount and duration of transgene expression. We hypothesize that transplantation immunosuppression can attenuate the post-transfection host-immune response to allow for improved gene transfer following adenoviral-mediated transfection. METHODS: We intratracheally transfected with adenovirus containing the beta-galactosidase gene and randomized the rats to either the immunosuppression group, receiving daily cyclosporine, azathioprine, and methylprednisolone, or the control group, receiving no immunosuppression. We evaluated transgene expression and post-transfection inflammation at time points ranging from 1 day to 5 weeks. RESULTS: Following transfection, control rats showed relatively low levels of transgene expression, which rapidly decreased to non-detectable levels. In contrast, immunosuppressed rats demonstrated significantly higher levels of transgene expression overall (p < 0.00005), peaking at almost 3 times that of the control group (p < 0.02), and showing prolonged and elevated transgene expression at 5 weeks (p < 0.02). On histologic sections of the lungs, immunosuppressed rats exhibited overall lesser grades of post-transfection inflammation. CONCLUSIONS: Transplant immunosuppression provides the means to attenuate the severe immune response to adenoviral-mediated gene transfection and thereby increase and prolong transgene expression.

Amiloride impairs lung water clearance in newborn guinea pigs.

To determine whether epithelial ion transport is physiologically important for lung water clearance after birth, the sodium transport inhibitor amiloride or its vehicle saline was given intratracheally to newborn full-term guinea pigs before the first breath. Guinea pigs given saline intratracheally breathed normally and had arterial O2 saturations (SaO2) greater than 94%. In contrast, guinea pigs that had an estimated 10(-4) M intra-alveolar concentration of amiloride had chest wall retractions and 88 +/- 3.6% (SD) SaO2 (P less than 0.01). Extravascular lung water (EVLW) per gram of dry lung weight 4 h after birth was significantly greater in newborns that received amiloride (8.3 +/- 1.1, n = 5) than in those that received saline (5.6 +/- 0.9, n = 7, P less than 0.01). The degree of perivascular fluid cuffing at 25 cmH2O inflation was quantitatively similar in amiloride- and saline-treated animals. The effect of amiloride was dose dependent. Intratracheal amiloride did not affect EVLW in 9-day-old guinea pigs. This study demonstrates that intratracheal amiloride before the first breath results in respiratory distress, hypoxemia, and an abnormally high EVLW. Epithelial sodium transport contributes normal lung liquid clearance after birth.

Validation of an orthotopic model of human lung cancer with regional and systemic metastases.

BACKGROUND: We developed an orthotopic model of human lung cancer that exhibits highly predictable regional and systemic metastases. This study examines the response of the model when treated with conventional and experimental chemotherapy. METHODS: NCI-H460 tumor fragments were implanted into the right caudal lung lobe of a nude rat. Treatment commenced 2 weeks later. We assessed response by comparing primary tumor and mediastinal lymph node weights, total body weight, and length of survival with untreated, tumor-bearing control animals. We also calculated the incidence of metastasis to kidney, bone, brain, and contralateral lung in treated versus untreated animals. RESULTS: Mitomycin and cisplatin showed broad activity against primary and metastatic disease. The matrix metalloproteinase inhibitor batimastat, low-dose cisplatin, and mitomycin significantly prolonged survival. High-dose cisplatin caused renal toxicity that shortened survival. Brain metastases did not respond to mitomycin, consistent with its poor blood-brain barrier penetration. CONCLUSIONS: Responses were similar to NCI-H460 in vitro data and consistent with clinical experience for these drugs. Drug-related toxicities similar to those seen in clinical practice were detected.

Intra-rectal injection of tumour cells: a novel animal model of rectal cancer.

The purpose of this study was to develop an animal model of rectal cancer. Three murine-derived cell lines, B16 melanoma, CT26 and MCA38 colon carcinoma, as well as the human colon cancer cell line LS174T were injected into the submucosa of the mouse rectum. Subcutaneous CT26 anbd B16 tumours and intra-caecal CT26 tumours served as controls for tumourigenicity of the cell lines. B16 melanoma produced a locally aggressive rectal tumour as well as skin and para-aortic lymph node metastases. CT26 produced local tumour when injected intra-rectally and colon tumours and liver metastases when injected into the caecum. MCA38 and LS174T intra-rectal injections resulted in large rectal carcinomas without metastases. We believe that growth of a colon cancer cell line in the rectum approximates the human disease more closely than other models of colorectal cancer. We would expect that the model could similarly be utilized to assess the effects of novel adjuvant treatments for rectal cancer as well as in the study of the tumour biology of rectal cancer.

Acute hyperesthesia after spinal trauma.

Four cases of acute hyperesthesia after spinal trauma are presented. An attempt is made to characterize the natural history of this syndrome. In the three cases with truncal sensory aberration, hyperesthetic zones developed only anteriorly. All four patients demonstrated spontaneous relief of pain within 2 weeks after injury. The pain was modified by transcutaneous stimulation in one case and by l-dopa in another case. It is suggested that the "lesion" responsible for the hyperesthetic response is partial damage to dorsal root fibers at a point medial to the dorsal root ganglion.

Effects of hyperbaric oxygen therapy on long-tract neuronal conduction in the acute phase of spinal cord injury.

To study the acute effects of hyperbaric oxygen ventilation (HBO) on long-tract function following spinal cord trauma, the authors employed a technique for monitoring spinal cord evoked potentials (SCEP) as an objective measure of translesion neuronal conduction in cats subjected to transdural impact injuries of the spinal cord. Control animals subjected to injuries of a magnitude of 400 or 500 gm-cm occasionally demonstrated spontaneous return of translesion SCEP within 2 hours of injury when maintained by pentobarbital anesthesia and by ventilation with ambient room air at 1 atmosphere absolute pressure (1 ATA). Animals sustaining corresponding injuries but receiving immediate treatment with HBO at 2 ATA for a period of 3 hours following impact demonstrated variable responses to this treatment modality. Animals sustaining injuries of 400 gm-cm magnitude showed recovery of translesion SCEP in four of five cases, while animals sustaining injuries of 500 gm-cm magnitude responded to HBO treatment by recovery of SCEP no more frequently than did control animals. When the onset of HBO therapy was delayed by 2 hours following impact, there appeared to be no demonstrable protective effect on long-tract neuronal conduction mediated by HBO alone. The observations suggest that HBO treatments can mediate preservation of marginally injured neuronal elements of the spinal cord long tracts during the early phases of traumatic spinal cord injury. These protective effects may be based upon the reversal of focal tissue hypoxia, or by reduction of tissue edema. HBO treatment markedly diminished the protective effects of HBO on long-tract neuronal conduction following traumatic spinal cord injury.

Improved engraftment of human tumours in SCID mice pretreated with radiation and anti-asialo GM1.

The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.

Cardiopulmonary function and pulmonary microemboli during arthroplasty using cemented or non-cemented components. The role of intramedullary pressure.

An experimental model was designed to investigate the role of intramedullary pressure on cardiopulmonary function and pulmonary pathology during arthroplasty using cemented and non-cemented components. Twenty-four dogs were divided randomly into three groups: a group that received a non-cemented implant in which low intramedullary pressure was generated, a group that received a cemented implant, and one that received bone wax and an implant; high intramedullary pressures were generated in the latter two groups. Bone wax was used to generate high intramedullary pressures without the use of bone cement. In the group with the non-cemented implant, few pulmonary microemboli and no significant cardiorespiratory changes were found. In the groups that received bone wax and an implant or the cemented implant, there were many pulmonary microemboli and significant cardiorespiratory changes, including decreased arterial oxygen tension, increased pulmonary arterial pressure, and increased intrapulmonary shunt fraction. There was no evidence that methylmethacrylate monomer was responsible for the cardiorespiratory changes in the group with the cemented implant.

High-volume, high-pressure pulsatile lavage during cemented arthroplasty.

To determine the efficacy of high-volume, high-pressure pulsatile lavage in the prevention of cardiopulmonary dysfunction and fat embolism during cemented arthroplasty, we studied twenty-eight mongrel dogs that had had a bilateral cemented arthroplasty. Significant increases in pulmonary-artery pressure and pulmonary vascular resistance, accompanied by decreases in arterial oxygen tension and increases in intrapulmonary shunt fraction (Qs/Qt), characterized cardiopulmonary dysfunction after bilateral cemented arthroplasty when no lavage was used. Low-volume, low-pressure manual lavage did not significantly alter these physiological changes, but there was a significant reduction in the number of fat emboli that were demonstrated in the lungs as compared with the no-lavage group. High-volume, high-pressure pulsatile lavage of the intramedullary cavity after reaming significantly reduced the changes in pulmonary-artery pressure, pulmonary vascular resistance, arterial oxygen tension, and intrapulmonary shunt fraction (Qs/Qt). In the pulsatile-lavage group, the number of fat microemboli that were found in the lungs was reduced to 25.7 per cent of those found in the no-lavage group. We concluded that meticulous high-volume, high-pressure pulsatile lavage reduces both pulmonary physiological derangements and fat emboli during bilateral cemented arthroplasty in dogs.

Long-term pain control by direct peripheral-nerve stimulation.

In 1970, we began implanting electrodes for prolonged stimulation of injured peripheral nerves to reduce chronic pain. Thirty-eight peripheral nerves in thirty-five patients have been stimulated with electrodes for a period ranging from four to nine years. Nineteen electrode systems were implanted in the upper extremity (eleven on the median nerve, six on the ulnar nerve, one on the median and ulnar nerves, and one on the median and radial nerves), with successful relief of pain in 52..6 per cent of the patients. Sixteen stimulators have been implanted on the sciatic nerve with a success rate for pain relief of 31 per cent. Failures in the lower extremity were found primarily in lesions of the posterior tibial nerve at the ankle. We speculate that the stress of weight-bearing and the anatomical position of the posterior tibial nerve may partially account for this rate of failure. Use of the electrode-implant systems required careful preoperative assessment by an experienced team, meticulous technique, and a mechanical system that tolerates stress. The location and characteristics of the lesion affect the response to electrical stimulation.