Biomedical subjects
Publications and source records attributed to G R Mason.
A hypotensive episode after rapid administration of a perfluorochemical emulsion, Fluosol-DA (20%), was associated with an immediate decrease in systemic vascular resistance but no significant change in pulmonary vascular resistance. Although the physiologic mechanism for this episode is unclear, the clinical implications are significant: the infusion rate of Fluosol-DA should not exceed 10 ml/min.
We have embarked upon a pilot study of photoradiation therapy (PRT) in the treatment of persistent or recurrent cancer of the head and neck utilizing the photosensitizing agent hematoporphyrin derivative (HPD). This treatment is based upon selective concentration of HPD within malignant tissue with resultant necrosis upon illumination with light of the appropriate wave length (630 nm). Patients entered in this trial have failed all forms of conventional therapy. Twenty-one patients with local recurrence were treated. Sites of recurrence were: tongue (9), nasopharynx (3), floor of mouth (2), soft palate (2), oropharynx (1), buccal mucosa (1), maxilla (1), larynx (1), basal cell nevus (1). There were six complete responses and twelve partial responses (greater than 50% reduction). These responses are clinically significant with some complete responses lasting over one year after a single course of therapy. Ten patients with cutaneous metastases from head and neck primary tumors were also treated. There were two complete responses and three partial responses. However, these patients rapidly developed new tumors in areas adjacent to those previously treated. Less than complete responses could be augmented by repeated applications of this technique. The success of this pilot study combined with the accessibility of head and neck primaries suggest that HPD-PRT should be given a clinical trial in early mucosal cancer of the head and neck region.
Current management of benign and malignant esophageal lesions has changed little in the past 25 years. Treatment of unresectable lesions has consisted primarily of exclusion and bypass procedures as well as prosthetic intubations for relief of dysphagia. A case of a Celestin tube fragmentation in a patient with unresectable esophageal carcinoma causing small bowel obstruction is presented. Diagnosis, management, and review of the literature are discussed. Recommendations for use of the Celestin tube in patients with good long-term prognoses include keeping a high index of suspicion for possible complications, close and regular radiographic and endoscopic follow-up, and early surgical intervention upon tube fragmentation.
To assess the role of portal hemodynamics in the development of postshunt encephalopathy, we studied 19 patients after small-diameter portacaval H grafting (SD-PCHG). We used contrast studies as well as technetium-labeled macroaggregated albumin injected into the portal vein to assess direction of portal flow. We then quantitated the mesenteric fraction of flow perfusing the liver by injecting macroaggregated albumin into a peripheral mesenteric vein tributary. We found that none of seven patients with prograde flow by both scintigraphy and angiography developed postoperative encephalopathy, but the incidence was 58% in the remaining patients (p = 0.02). The fraction of mesenteric flow perfusing the liver after SD-PCHG was 12% +/- 4%, but this did not significantly correlate with encephalopathy rates. We conclude that after SD-PCHG, prograde portal flow minimizes encephalopathy rates. Although encephalopathy occurs in patients with predominantly reversed flow, a subgroup of patients with reversed flow remain without symptoms. The absolute fraction of mesenteric flow perfusing the liver has less influence on encephalopathy rates than has direction of portal flow. This study identifies a complex relationship between portal hemodynamics and encephalopathy.
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Clinical observations suggest that patients with portal hypertension are more prone to erosive gastritis. To test this hypothesis we investigated gastric mucosa of rats with portal hypertension (produced by staged portal vein occlusion) and sham-operated controls before and after intragastric taurocholate. Portal pressure was 36 +/- 3 cm saline in portal hypertensive rats compared with 16 +/- 2 cm in controls (P less than 0.01). Before taurocholate no macroscopic or histologic spontaneous mucosal damage was present, but portal hypertensive rats had extensive submucosal edema. Three hours after intragastric taurocholate (2 ml, 80 mM in 0.1 N HCl), macroscopic injury comprised 13.7 +/- 1.1% of mucosal surface in portal hypertensive rats compared with 3.6 +/- 0.6% in controls (P less than 0.01) confirmed also by histologic morphometry. H+ back-diffusion was 402 +/- 40 microEq/h in portal hypertensive rats and 217 +/- 30 microEq/h in controls (P less than 0.01). We conclude taurocholate induced gastric mucosal injury is enhanced by portal hypertension. Greater H+ back-diffusion in portal hypertensive rats suggests increased mucosal permeability contributed by submucosal edema. We confirm quantitatively in an experimental model that portal hypertension predisposes to gastric mucosal injury.
The purpose of this study was to investigate the interaction of heat and chemotherapy in experimental whole body hyperthermia (WBH). A vascular technique of extracorporeal perfusion was employed to rapidly elevate body temperature in rabbits carrying the transplantable VX-2 carcinoma. Hyperthermia (greater than 41 degrees C) was achieved in a mean time of 28 minutes. Tumor-bearing rabbits receiving WBH alone exhibited poor mean survival (14 days) relative to untreated tumor-bearing animals (32 days) and the group receiving IV Cis-platinum alone (50 days) (NS, p less than .05 respectively). WBH with Cis-platinum was intermediate in terms of mean survival (30 days, NS) between the WBH alone and Cis-platinum alone groups. In this experimental model we have determined WBH to be a detrimental form of cancer therapy. Its action appears to enhance tumor proliferation, resulting in rapid animal demise. In light of these findings a reevaluation of clinical WBH may be warranted.
Transcutaneous oxygen sensor values reflect peripheral oxygen tensions. During shock and resuscitation, transcutaneous oxygen sensor values depend on peripheral blood flow, and, therefore, reflect cardiac output and oxygen delivery. Transcutaneous oxygen sensor monitoring, therefore, should be quite useful when caring for acutely ill patients; data from 20 surgical emergency department patients support this hypothesis. A normal initial transcutaneous oxygen sensor value of greater than 60 torr, as found in 11 of our patients, implied relatively normal oxygenation and circulation. A low initial transcutaneous oxygen sensor value of less than 60 torr implied deficits of either arterial oxygenation or of perfusion (these can be distinguished by an arterial blood gas determination). In addition, transcutaneous oxygen sensor was useful for continuous monitoring during resuscitation. Successful correction of hypoxia and perfusion deficits results in increased transcutaneous oxygen sensor values. Failure of the transcutaneous oxygen sensor value to increase during resuscitation implies ongoing deficits of tissue oxygenation.
In a series of experiments in anesthetized dogs, the origin and mechanism of reduced renal blood flow (RBF) during acute portal hypertension was investigated. With acute superior mesenteric vein (SMV) occlusion and normalization of cardiac hemodynamics RBF remained reduced at 66 +/- 14 ml/min compared to baseline of 160 +/- 25 ml/min (P less than 0.01). Neither acute superior mesenteric artery occlusion, nor acute hepatic portal hypoperfusion with normal SMV pressures maintained by SMV-caval shunt, resulted in reduction of RBF. Cross-perfusion studies failed to produce alterations of RBF in recipient dogs from donor dogs with SMV occlusion, reduced RBF, and normal cardiac outputs. Finally, splanchnic ganglionectomy prevented RBF reduction during SMV occlusion after volume restoration. We conclude that reduced RBF during acute portal hypertension is a result of an intestinal-renal neurogenic reflex initiated by intestinal venous congestion.
Small-diameter protacaval H-grafts, 10, 12, or 14 mm, were constructed in 29 cirrhotic patients with previous or active variceal hemorrhage. When 10 mm grafts were used in combination with portal collateral outflow ligation, varying degrees of prograde portal flow were maintained in 50% of the patients. When shunt size was greater, prograde flow was lost in more than 90%. The incidence of spontaneous postoperative encephalopathy was 11% in patients with prograde flow, compared with 50% in those with retrograde flow (p = 0.05). It is concluded that maintaining prograde portal flow after portacaval shunt is essential in minimizing postoperative encephalopathy. Prograde portal flow may be achieved in 50% of patients using 10 mm PTFE portacaval H-grafts combined with portal collateral ligation.
The patient with an acute scrotal swelling may be misdiagnosed and either have unnecessary surgery or not have necessary surgery. Radionuclide imaging has been used on 33 patients with scrotal swellings and has been found to be an easy, cheap and painless investigation with a high degree of accuracy of diagnosis. It is recommended as a useful diagnostic tool in cases of scrotal swelling of doubtful aetiology, particularly when emergency surgery is being considered.
An in situ rabbit preparation was used to characterize the manner in which edema fluid enters the airways when left atrial pressures are elevated. The airways were initially filled with fluid to minimize retrograde flow of edema fluid into the alveoli. The airway solution contained 125I-albumin and in some studies [14C]sucrose, and the lungs were perfused with a comparable solution which contained albumin labeled with Evans blue dye and 99mTc-diethylenetriaminepentaacetate (DTPA) or 99mTc-sulfur-colloid particles (0.4-1.7 micron diam). After 30 min of perfusion, fluid was pumped from the airways into serial tubes. When left atrial pressures were low, there was very little transfer of labels detectable between the airway and perfusate solutions. However when left atrial pressures were increased to either 15 or 22 cmH2O, fluid entered the airways containing approximately the same concentrations of Evans blue dye and 99mTc-DTPA as those present in the perfusate. In contrast, the concentration of colloid particles averaged less than 5% perfusate concentrations, indicating that the fluid had not escaped through a tear in the barriers separating the vascular and airway compartments. Concentrations of the perfusate fluid and indicators were highest in the initial samples pumped from the airways. These observations suggest that some of the fluid entering the airways may be derived from peribronchial cuffs or that there are marked regional differences in edema formation from alveoli.
A radioaerosol procedure using 99mcTc-DTPA (diethylene triamine penta acetate) was used to evaluate the permeability of the pulmonary epithelium in smokers and nonsmokers. The average clearance of this indicator from the lungs of smokers without significant airway obstruction exceeded that found in normal subjects by an average factor of more than five. This abnormality was observed throughout all lung regions. 99mTc-DTPA clearance decreased rapidly during the week after smoking was discontinued. It is concluded that smoking results in a rapidly reversible increase in pulmonary epithelial permeability.
The present study was performed primarily in order to determine whether gastric mucosa of rats with portal hypertension has different functional and histologic features when compared with controls, and second to quantitate and compare morphologic and functional changes after exposure to topical ethanol. Portal hypertension was produced by staged portal venous occlusion, and in these animals portal pressure was 32 +/- 2 cm saline compared with 18 +/- 2 cm in sham-operated controls (p less than 0.005). Before ethanol, portal hypertensive rats compared with controls had significantly higher luminal pH (2.9 +/- 0.3 vs. 1.9 +/- 0.1), increased H+ back-diffusion (loss of 138 +/- 10 vs. 57 +/- 16 microEq H+/h), lower potential difference (8 +/- 1 mV lower than controls), and extensive submucosal edema (submucosal thickness 325 +/- 25 vs. 138 +/- 18 micrometers). After 3 h of exposure to 2 ml intragastric absolute ethanol, the area of macroscopic hemorrhagic mucosal injury was significantly greater in portal hypertensive rats than in controls (34.0 +/- 8.7% vs. 7.6 +/- 2.1%), confirmed histologically by the greater number of deep hemorrhagic necrotic lesions and extent of mucosal length involved. Furthermore, after ethanol, portal hypertensive rats compared with controls had significantly increased gastric volume (14.4 +/- 1.5 vs. 8.3 +/- 0.6 ml), Na+ (86.6 +/- 8.0 vs. 64.6 +/- 8.0 mEq/L), pH (7.1 +/- 0.3 vs. 4.3 +/- 0.4), H+ back-diffusion (loss of 309 +/- 41 vs. 207 +/- 33 microEq H+/h), and protein and blood loss (100% increases over controls). These results indicate that gastric mucosa of portal hypertensive rats has distinctive functional and histologic abnormalities that can explain its increased susceptibility to erosive injury after ethanol. This study quantitatively confirms in an animal model the clinical observations that portal hypertension may predispose to severe gastric mucosal injury.
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The intent of this study was to determine whether or not local control and/or cure of rabbits bearing the VX-2 carcinoma could be achieved with regional hyperthermia and chemotherapy. A model of isolation-perfusion used cis-diamminedichloroplatinum(II) (DDP). Five different experimental groups were studied, each group receiving progressively smaller tumor inocula and shorter treatment intervals. Although local control and cure improved as the tumor inocula became smaller and treatment interval became shorter, there was no benefit demonstrated when compared to sham-operated animals. DDP appeared to be well tolerated in animals perfused as normothermic temperatures. However, animals perfused at hyperthermic temperature with DDP experienced necrosis of normal as well as neoplastic tissue, resulting in early demise of the animal. This final observation suggests that the amount of DDP utilized in clinical isolation-perfusion should be approached with caution.
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We conducted a trial of photoradiation therapy of cancer at the University of California at Irvine. The basis of this technique is a photochemical reaction between an i.v.-injected material, hematoporphyrin derivative, and red light (wavelength, 630 nm). Hematoporphyrin derivative localized in malignant tissue, resulting in selective destruction of cancer cells upon illumination with red light. One hundred twenty-eight sites of recurrent cancer or premalignant lesions were treated in 37 patients. Of this group, 35 patients had recurrent cancer refractory to conventional therapy, and two had premalignant lesions. Favorable responses were achieved in 67% of the sites treated. The dose of hematoporphyrin derivative used in this study ranged from 2 to 5 mg/kg with the majority of patients receiving 3 mg/kg. Total light dose administered appeared to be the most critical parameter evaluated. Light doses in excess of 20 J/sq cm generally resulted in blistering and necrosis of intact skin, while no appreciable increase in response was observed. Photoradiation therapy has demonstrable efficacy in cancer therapy and avoids much of the morbidity of current conventional techniques.