Laser photoradiation therapy of cancer.

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.

Experimental hyperthermic isolation-perfusion using cis-diamminedichloroplatinum(II).

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.

Neonatal pancreatic beta-cell hyperplasia: report of a case with failure of diazoxide and benefit of early subtotal pancreatectomy.

A newborn infant with pancreatic beta-cell hyperplasia had persistent hypoglycemia due to hyperinsulinism. After medical management, including the use of diazoxide and constant glucose infusions had proved ineffective, a subtotal pancreatectomy was curative. Cumulative experience seems to indicate that there should be little delay in performing a subtotal pancreatectomy when aggressive medical management cannot maintain normoglycemia in a neonate.

Small solute clearance from the lungs of patients with cardiogenic and noncardiogenic pulmonary edema.

The regional clearance of 99mTc-diethylenetriamine penta-acetate (99mTc-DTPA) from the lungs was measured in 14 patients with noncardiogenic pulmonary edema, six patients with acute pulmonary edema secondary to heart failure, and 29 normal subjects. The radionuclide was delivered in an aerosol which was inhaled for 120 seconds, and the subsequent decline of radioactivity from the lungs was monitored for seven minutes over each of six peripheral regions of interest with a computerized scintillation camera. The average 99mTc-DTPA clearance of these regions was accelerated above the 98 percent confidence limits in all but three of the patients with noncardiogenic edema. The mean clearance value in this group of patients was significantly greater than those in normal subjects or patients with cardiogenic pulmonary edema. Clearances returned toward normal in each of seven subjects who improved clinically. Only one of the patients with cardiogenic pulmonary edema had an elevated average clearance rate, and the mean clearance for this population was not statistically greater than normal. This procedure appears to detect increased epithelial permeability caused by lung injury and may help distinguish between cardiogenic and noncardiogenic pulmonary edema.

Rapidly reversible alterations of pulmonary epithelial permeability induced by smoking.

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.

Fragmentation of a Celestin tube causing intestinal obstruction. Case report and review of the literature.

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.

111-indium-DTPA-IgG lung imaging in patients with pulmonary and HIV infection.

111-Indium-DTPA-IgG (111In-IgG) is a new radiopharmaceutical that has been evaluated for the detection of infection without the need for in vitro cell labeling. We prospectively studied this agent in 33 patients suspected of having lung infections, most of whom also had HIV infection, and three patients with HIV infection and diarrhea without lung disease. Anterior and posterior lung images in the upright position were obtained within 24 h after intravenous administration of 2 mCi of 111In-IgG and were read in a blinded fashion by two nuclear medicine physicians. Of 29 patients suspected to have Pneumocystis carinii pneumonia (PCP), the diagnosis was confirmed by bronchoalveolar lavage in 18. Diffusely increased lung uptake of 111In-IgG was found in 17 of 18 patients who had PCP and was normal in 10 of 11 patients without PCP. The intensity of 111In-IgG uptake was related to sever gas exchange abnormality. Two patients with apparent bacterial lung infections had focal accumulation of 111In-IgG while two patients with minor radiographic abnormalities had no increased uptake. Normal lung uptake also occurred in two of three HIV-positive patients who had diarrhea and no lung disease. 111In-IgG appears to be useful in the detection of PCP and other pulmonary infections.

Comparison of continuous-wave lasers for endarterectomy of experimental atheromas.

The standard surgical lasers, argon ion, neodymium-yttrium aluminum garnet, and carbon dioxide, are often operated as continuous wave lasers with specific uses. Clinical trials of laser therapy for arteriosclerotic cardiovascular disease are underway with all three lasers. Therefore, we compared these three lasers under controlled experimental conditions. A thoracoabdominal exploration was performed in 17 arteriosclerotic rabbits. The aorta was isolated, heparin administered, and multiple endarterectomies were performed in each rabbit with each of the lasers. A line of laser craters was created at the proximal and distal ends of an atheroma. Continuous-wave laser radiation was used to connect the craters and thereby form proximal and distal end points. The plaques were dissected free from the aorta with laser light and the end points were fused by laser. The aortas were removed for light microscopy and the animals were killed. The endarterectomy surfaces and end points were serially sectioned and graded according to light microscopic findings (1 = worst, 4 = best). Argon ion laser endarterectomy (N = 16) required 106 +/- 10 J/cm2. The surface score was 3.5 and end point score 3.4. Neodymium-yttrium aluminum garnet laser endarterectomy (N = 13) required 1,289 +/- 115 J/cm2 with a surface score of 2.4 (p less than 0.001 from argon ion) and an end point score of 1.3 (p less than 0.001 from argon ion). Carbon dioxide laser endarterectomy (N = 9) required 30 +/- 5J/cm2 with a surface score of 2.0 (p less than 0.001 from argon ion) and and end point score of 1.6 (p less than 0.001 from argon ion). Perforation occurred in one of 16 argon ion studies (technical error, not laser), in 11 of 13 neodymium-yttrium aluminum garnet studies, and in six of nine carbon dioxide studies. This study demonstrates that of the currently available clinical continuous-wave lasers, the argon ion laser is superior for endarterectomy of experimental atheromas.

Pyloric motor response to sympathetic nerve stimulation in dogs.

Through this study we evaluated the effect of electrical stimulation of the greater splanchnic nerve on gastroduodenal motility in anesthetized dogs. The majority of stimulations (at a frequency of 10 Hz for 5 msec at a strength of 10V for a train of 10 sec) produced contractions in the gastric antrum and pylorus and relaxation in the duodenum. The antral, pyloric, and duodenal motor responses were unaffected by cervical vagosympathectomy, thoracic vagotomy, and adrenalectomy. Administration of phentolamine, propranolol, or hexamethonium and pretreatment with reserpine failed to affect the contractile gastroduodenal motor response. The inhibitory motor response in the duodenum was also unaffected by these surgical procedures and administration of drugs. After atropine administration, contractions induced by splanchnic nerve stimulation were abolished in the pylorus, as well as in the antrum and duodenum. Tetrodotoxin also abolished the gastroduodenal motor response. The greater splanchnic nerve contains an excitatory cholinergic pathway to the musculature of the pylorus.

Selective impairment of nutrient absorption from intestines with chronic venous hypertension.

Malnutrition is frequently associated with advanced cirrhosis. To investigate the role of portal hypertension in nutritional impairment, we developed an animal model to isolate and characterize the effects of chronic intestinal venous hypertension on intestinal nutrient absorption. We performed mesenteric arteriovenous anastomosis combined with portal vein banding in rats. Hepatic architecture and excretory function (bile flow and bile salt output) were unaltered, while severe and persistent intestinal venous hypertension was produced. We then measured in vivo absorption rates of three test nutrients (vitamin D3, valine, and tryptophan) and water. Vitamin D3 absorption was significantly impaired by intestinal congestion, while amino acid absorption was unaffected. Splanchnic hypertensive rats absorbed less water than controls. We conclude that chronic intestinal venous hypertension alone selectively impairs nutrient absorption.

Clinical implications of portal hemodynamics after small-diameter portacaval H graft.

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.

New evidence for active sodium transport from fluid-filled rat lungs.

The hypothesis that fluid reabsorption from the air spaces is mediated at least in part by active transport of Na+ was investigated in six sets of experiments conducted in isolated fluid-filled rat lungs. Fluid reabsorption was monitored by following the changes in the air space concentration of labeled albumin. We found that incorporation of bicarbonate rather than a nonvolatile buffer (N-2-hydroxy-ethylpiperazine-N'-2-ethanesulfonic acid) in the air space solution more than doubled the rate of fluid reabsorption. Addition of 10(-4) M amiloride to the air space solution reduced the rate of fluid reabsorption over a 2-h experiment from 1.2 +/- 0.1 to 0.7 +/- 0.1 ml and decreased reabsorption of both labeled and unlabeled Na+ from the air spaces. To show that Na+ could be reabsorbed from the air spaces even if the concentrations of Na+ in the perfusate increased above those in the air space, mannitol (150 mM) was added to the perfusate and air space solutions and the concentrations of Na+ and Cl- were reduced to 90 and 60 mM, respectively. Mannitol diffuses across the pulmonary epithelium very slowly, and it osmotically restrained the movement of water out of the air spaces. Na+ concentrations in the perfusate increased by 10 +/- 2 mM, but concentrations in the air space remained unchanged. Despite an increasingly unfavorable concentration gradient for Na+, 0.2 mmol Na+ and 0.6 ml water were reabsorbed from the air spaces in 2 h. Ouabain (10(-4) M) did not appear to slow fluid reabsorption in the presence of mannitol, but it reduced K+ secretion into the air spaces and increased K+ appearance in the perfusate in a manner consistent with inhibition of Na+-K+-adenosinetriphosphatase at the basolateral surface of the epithelial cells. Fluid reabsorption was not altered when the lungs were exposed to a hypotonic solution (185 mM), but secretion of K+ into the air spaces was accelerated and K+ was lost from the perfusate. These experiments are consistent with active Na+ transport from the air spaces.

Pulmonary epithelial sieving of small solutes in rat lungs.

Transport and consumption of glucose from the air spaces of isolated, fluid-filled lungs can result in significantly lower glucose concentrations in the air spaces than in the perfusate compartment (11). This concentration difference could promote the osmotic movement of water from the air spaces to the perfusate, but the rate of fluid extraction from the air spaces would then be limited by the rates of electrolyte transport through the epithelium. In the present study, measurements were made of solute and water losses from the air spaces of fluid-filled rat lungs and the transport of these solutes and water into the vasculature after addition of hypertonic glucose or sucrose to the perfusate. Increases in the concentrations of Na+, Cl-, K+, and labeled mannitol in the air space were initially comparable to those of albumin labeled with Evans blue. Similarly, decreases in electrolyte concentrations in the perfusate were comparable to those of labeled albumin, indicating that very little solute accompanied the movement of water out of the lungs. Nor was evidence found that exposure of the vasculature to hypertonic glucose resulted in an increase in the rate at which fluid was reabsorbed from the air spaces over a 1-h interval, aside from an initial, abrupt loss of solute-free water from the lungs. These observations suggest that perfusion of fluid-filled lungs with hypertonic solutions of small solutes results in the extraction of water from the air spaces and pulmonary parenchyma across membranes that resist the movement of electrolytes and other lipophobic solutes.

Appropriate background correction for DTPA aerosol clearance.

Measurement of the clearance rate of inhaled aerosols of 99mTc-diethylenetriamine pentaacetic acid (DTPA) from distal airway to pulmonary capillary is a sensitive technique for the detection of lung injury. As the solute diffuses across the blood-gas barrier, the concentration in circulating blood increases, giving rise to a background signal superimposed on the signal from residual DTPA in the airway. Background subtraction is conventionally based on the thigh, but this tissue has the disadvantage in that its composition, in terms of the relative volumes of its extracellular extravascular and intravascular compartments (a ratio of approximately 4:1), is quite different from that of the lung (<1:6). With comparison to the thigh, we examined alternative regions for background, liver, and cranium, which have extravascular-to-intravascular compartment ratios much closer to these for the lung, to determine the most appropriate background for correction of the pulmonary signal. From 1 min after intravenous injection of 99mTc-DTPA, the time-activity curves recorded by a gamma camera over the liver and lung in a group of otherwise normal cigarette smokers decreased up to 30 min after injection, with time courses that could essentially be superimposed on each other; the curve recorded over the thigh with a separate scintillation probe continued to increase. The curve recorded over the cranium had a time course similar to that for the liver and lung. Following aerosol inhalation, the lung clearance rates over the initial 7 min when background subtraction was used, based on the liver, cranium, and thigh were, respectively, 4.9 +/- 2.9, 4.7 +/- 2. 6, and 5.4 +/- 3.4 (SD) %/min, compared with 4.1 +/- 2.2%/min without subtraction. The corresponding values based on 30 min of data were 3.3 +/- 1.4, 3.4 +/- 1.4, 4.2 +/- 2.3, and 2.8 +/- 1. 0%/min. When the liver was used for background, the lung clearance curves were clearly multiexponential, whereas thigh correction tended to give curves that were monoexponential or even convex upward on semilogarithmic axes. With an appropriate region for background, the true shape of a lung curve can be identified, which permits the study of an intervention on the clearance while it is in progress. The intravenous DTPA, required for calibrating the background regions, can be given before inhalation of the tracer.

Movement of ions and small solutes across endothelium and epithelium of perfused rabbit lungs.

In situ and isolated fluid-filled rabbit lungs were used to study the transport of indicators between the air space and vascular compartments. These indicators were placed in either the perfusate or air spaces and samples were collected from the perfusate at intervals during a 1-h perfusion period. At the end of the hour, fluid was pumped out of the air space compartment into serial tubes and indicator concentrations were determined in both the air space and perfusion fluids. One hour after introducing the indicators into the air space, the relative decreases in solute concentration were (arranged from the greatest to the least decline): [14C]urea greater than 36Cl- = 125I- greater than 22Na+ greater than [3H]mannitol. The relative rates at which the indicators appeared in the perfusate were similar. When the indicators were placed in the perfusate, a similar relationship was observed in the increase in air space concentrations, but the loss of 22Na+ from the perfusate was similar to those of 36Cl- and 125I-. Losses of all indicators from the perfusate were two or more times those from the air spaces, and although the loss of [3H]mannitol from the perfusate was similar to that of 22Na+ for about 30 min, subsequent loss was much slower. Very little 125I-albumin traversed the tissue barrier, and the small changes in the concentrations of 125I-albumin in the air spaces suggested that little fluid movement had occurred. These studies suggest that the epithelium is less permeable to solutes than the endothelium and permits passage of anions at a faster rate than 22Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortocystoduodenal fistula: rare complication of pancreatic pseudocyst.

An upper gastrointestinal tract hemorrhage resulting from an aortocystoduodenal fistula developed in a patient with a pancreatic pseudocyst. The fistula was exposed through a duodenotomy, necrotic material was debrided from the pseudocyst and the aortic wall, the aortic defect was closed primarily, and the pseudocyst was drained through a cystoduodenostomy. The case is discussed as a rare hemorrhagic complication of pancreatic pseudocysts and as an illustration that under certain circumstances of infection in areas where aortic bypass can be difficult to perform, primary vascular repair can be a successful method of managing aortoenteric fistulas.

Perfluorocarbon infusion in bleeding patients refusing blood transfusions.

Six severely anemic surgical patients who refused blood products were treated with a perfluorochemical (PFC) emulsion (Fluosol-DA 20%). When these patients received high inspired oxygen concentrations, the emulsion resulted in moderate increases of arterial oxygen content but considerable increases of oxygen consumption, suggesting improved microcirculatory oxygen distribution. The mean +/- SD percentages of consumed oxygen transported by dissolved oxygen in PFC and PFC plus plasma emulsions were 22% +/- 5% and 60% +/- 12%, respectively. Several adverse clinical effects were seen, however, including transient decreases in leukocyte counts, hypotension, and abnormal hepatic and pulmonary function.

Initial trial of argon ion laser endarterectomy for peripheral vascular disease.

In the initial of open laser endarterectomy, 16 patients underwent 18 reconstructions for claudication (13 patients), rest pain (3 patients), and gangrene (2 patients). The mean (+/- SD) preoperative ankle arm index was 0.53 +/- 0.18. The laser endarterectomies were aorto-bi-iliac (1 patient), iliac (1 patient), superficial femoral (7 patients), profunda femoral (7 patients), and popliteal-posterior tibial (2 patients). All operations included surgical exposure, vascular control, administration of heparin, and an arteriotomy. Atheromas were dissected from arteries with argon ion laser radiation (power, 1.0 W). End points were welded with laser light. Arteries were closed primarily. The laser endarterectomies were 6 to 60 cm long and required 168 J to 2447.5 J. All patients had symptomatic relief, with a postoperative ankle arm index of 0.97 +/- 0.10. There were no arterial perforations from laser radiation. Surgical complications included early thrombosis requiring thrombectomy (3 patients) and hematoma requiring evacuation (1 patient). The laser endarterectomies have an 88% patency at 1 year. Open endarterectomy can be performed with laser radiation. A larger clinical trial is necessary to define the indications for laser endarterectomy in peripheral vascular disease.

Description of a continent jejunal gastrostomy.

A new technique of permanent gastrostomy interposes a vascularized jejunal conduit with an intussuscepted valve between the stomach and abdominal wall, creating a "continent jejunal gastrostomy". In a series of dogs undergoing gastrostomy, the continent jejunal gastrostomy functioned well, with no leakage, and was superior to gastric tube gastrostomy in this regard. Furthermore, there was no evidence of marginal ulceration. A patient who underwent continent jejunal gastrostomy has an excellent one-month result.

Diagnosis of traumatic cardiac contusion.

Cardiac contusion following blunt chest trauma remains a diagnostic problem because of a lack of sensitive diagnostic tests. This study evaluated thallous chloride Tl 201 single-photon-emission computed tomography in a series of 48 patients following blunt chest trauma. Of the 48 patients, 23 had normal scans. None of these patients proved to have serious arrhythmias during three days of continuous monitoring. Of 25 patients with abnormal or ambiguous studies, five (20%) developed serious arrhythmias requiring therapy. Single-photon-emission computed tomography scanning thus was sensitive in indicating that group of patients at risk of serious arrhythmias, and may therefore prove to be a useful screening test to determine the need for hospitalization and arrhythmia monitoring following blunt chest trauma.