Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation

Successful adoptive cancer immunotherapy presumably depends on the accumulation of tumoricidal leukocytes at the sites of tumor growth. Large numbers of lymphokine-activated killer (LAK) cells can be generated in vitro by growth in high concentrations of interleukin-2 (IL-2), but relatively few arrive at the tumor site after intravenous injection. We hypothesize that the delivery of LAK cells to tumor sites may be augmented by previously demonstrated lymphocyte-recruiting factors, including activated macrophage products such as interleukin-1 (IL-1) and tumor necrosis factor. 111Indium-labeled LAK cells were injected intravenously into syngeneic mice bearing the macrophage activator endotoxin (LPS) in one hind footpad, and saline solution was injected into the contralateral footpad. Significantly more activity was recovered from the LPS-bearing footpad at all times during a 96-hour period. Recombinant IL-1 also attracted more LAK cells after injection into tumor-free hind footpads. Furthermore, LAK cells preferentially homed to hind footpads that were bearing 3-day established sarcomas after intralesional injections of LPS, IL-1, or tumor necrosis factor when compared with contralateral tumor-bearing footpads injected with saline solution alone. In preliminary experiments, mice with hind-footpad tumors appeared to survive longer after combined systemic IL-2 and LAK therapy if intralesional LPS was administered. These studies demonstrate that macrophage activation factors that have been shown capable of attracting circulating normal lymphocytes can also effectively attract LAK cells from the circulation. By the stimulation of macrophages at the sites of tumor growth, more LAK cells can be attracted. It is hoped that by "focusing" the migration of LAK cells to tumors, LAK cells and IL-2 would effect tumor regression more efficiently and with less toxicity.     

How Many Swallows Are Required to Establish Reliable Esophageal Peristaltic Parameters in Normal Subjects? An On-Line Computer Analysis

Esophageal manometric parameters are often examined using from four to 10 or more swallows to obtain a manometric profile without addressing the question of the reproducibility of these data. We asked the question of "how much is enough?" by statistically comparing five sets of 10 wet swallows (5 ml) each separated by 20 min in eight volunteers using constant infusion manometry. Peristaltic waves were evaluated for amplitude, duration, and velocity using an on-line computer program. Statistical analyses included analysis of variance and the Newman-Keuls test for uniformity among sets of swallows. The sets of 10 swallows showed no evidence of a training effect over time. Less than 5% of all comparisons (Newman-Keuls) showed significant differences. Using 5% variability outside of 1 SD as a cutoff (95% confidence interval) amplitude of normal wet swallows could be adequately defined by more than or equal to five swallows and velocity by more than or equal to seven swallows. Duration shows the greatest overall variability and required more than or equal to eight swallows for accurate assessment. These data suggest that at least five to eight wet swallows should be performed to describe "typical" manometry parameters for normal subjects.     

AUR Memorial Award. Two computer models for selection of optimal magnetic resonance imaging (MRI) pulse sequence timing

Two computer modeling techniques have been developed that aid in the selection of optimal magnetic resonance imaging (MRI) pulse sequences and timing intervals for specific clinical situations. The "parameter sensitivity" technique provides a means of selecting three separate MRI scans which are individually sensitive to changes in each of the three NMR tissue parameters N, T1, and T2. The "contrast" technique allows selection of a single optimal MRI sequence using the expected changes in all three tissue parameters simultaneously. Excellent correlation is demonstrated between the models and images obtained in a normal volunteer and in a patient with multiple sclerosis. The two methods compliment each other; the parameter sensitivity method is most useful in situations where subtle changes in tissue parameters are expected, whereas the contrast method is suited to circumstances where large differences in tissue parameters are anticipated and the magnitude and direction of these changes are known.     

Brain-specific protein C activation during carotid artery occlusion in humans

BACKGROUND AND PURPOSE: Activation of plasma protein C (PC) zymogen by thrombin-thrombomodulin at the endothelial surface is an important endogenous antithrombotic mechanism. It is unknown whether activated protein C (APC) is generated in vivo in the cerebrovasculature, because there is only limited thrombomodulin expression in human brain vascular endothelium. Therefore, we tested the hypothesis that carotid occlusion produces brain-specific PC activation. METHODS: Blood samples were simultaneously collected from the ipsilateral internal jugular vein and radial artery before and during carotid cross-clamping and on "de-occlusion" in 8 awake patients undergoing routine carotid endarterectomy. Plasma PC zymogen and circulating APC levels were measured using enzyme immunocapture assay and expressed as percent of pooled plasma controls. RESULTS: Internal jugular vein APC levels increased 28% exclusively during carotid occlusion and then decreased 32% with de-occlusion (F=8.1, P<0.005). PC zymogen increased only 5.9% with occlusion (F=6.3, P<0.02), consistent with hemoconcentration. There were no changes in radial artery PC or APC levels. CONCLUSIONS: These findings demonstrate brain-specific protein C activation in humans during carotid occlusion and suggest a protective role for endogenous APC generation during cerebrovascular occlusion.     

Non-destructive evaluation of membrane lung gas exchange performance

This paper describes a method of evaluating the gas exchange effectiveness of hollow fiber oxygenators utilizing gas on both sides of the membrane. The goal of the study was to develop an evaluation technique which was accurate, reliable, and did not harm or contaminate a new, sterile oxygenator. Three pediatric oxygenators were tested and compared: the Medtronic Minimax Plus, the Terumo Capiox 320, and the Sorin Masterflo 34 (all with rated blood flows of 2-2.5 L/min). Gas entering the "blood" side was a mixture of CO2, O2, and N2 in a mixture matching typical venous blood partial pressures. The "blood" flows used were 0.5, 1, 1.5, or 2 L/min. Gas entering the gas port had an FiO2 of 0.4 flowing at 0.5, 1, 1.5, 2, 2.5, 3, or 3.5 L/min. Fractional contents of CO2 and O2 at all inlets and outlets were determined using a gas analyzer and converted to partial pressures. Efficacy indices and gas transfer rates were calculated and compared. Of the devices studied, the Masterflo 34 had the highest gas transport rates and effectiveness followed by the Minimax-Plus and the Capiox 320. Reversing the direction of the flow through the "blood" phase of the Minimax-Plus greatly changed its gas exchange effectiveness. The techniques described in this study should allow for a more uniform and consistent evaluation of gas exchange by membrane lungs which can be made inexpensively and relatively quickly. In addition, these methods should allow manufactures to evaluate gas exchange effectiveness and transfer rates of individual units during production as well as reduce the complexity involved when evaluating newly developed oxygenators.     

Changes in physical endurance following a 3-months' exam period

The question was raised to what extent in the course of a three-month examination period as a time of increased psychic stress, depending upon the distinction of the personal peculiarity "fear of examinations" of the students, reductions of the physical efficiency develop. On the basis of the lactate efficiency curves a significant decrease in vitality after a three-month examination period was proved. The determination of the efficiency in the aerobic-anaerobic transitional zone renders possible an exact evidence, independent upon motivation. According to the results the formation of the curriculum has a determining influence on the physical efficiency, however, not the personal peculiarity "fear of examinations".     

Perinatal lethal hypophosphatasia; Clinical,radiologic and morphologic findings

Clinical, radiographic and morphologic analysis of nineteen cases of perinatal (lethal) hypophosphatasia was performed. Three families each had two affected offspring. All of the patients had lethal short limb dwarfism with very soft calvaria. Other clinical findings included polyhydramnios, blue sclerae and spurs in the mid-portion of the forearms and lower legs. Considerable variability was found in the skeletal radiographs. In addition to the well known radiographic features such as generalized decrease in the size of ossified bones with some bones not ossified at all, other changes observed included: 1) marked variability in the amount of bone ossification; 2) variability between patients as to which bones were most severely affected; 3) unusually dense, round, flattened, butterfly shaped; and saggitally clefted vertebral bodies; 4) variability in femoral shape including chromosome like, campomelic like, and shortening with or without metaphyseal cupping or irregularities; 5) osteochondral projections (Bowdler spurs) of the midshaft of the fibula and ulna. Recognition of the marked clinical and radiographic variability in this autosomal recessive lethal skeletal dysplasia is important for accurate genetic counseling and prenatal diagnosis.     

Ergebnisse der selektiv proximalen vagotomie nach 13 Jahren

Zusammenfassung Es wird über die Langzeitergebnisse von 216 Patienten berichtet, bei denen zwischen 1970 und 1978 wegen eines Ulcus duodeni eine selektiv proximale Vagotomie (SPV) vorgenommen wurde. Die mittlere Nachbeobachtungszeit beträgt 12,8 Jahre (8,3–15). 26 Patienten erlitten ein symptomatisches Ulkusrezidiv (12%)4–135 Monate postoperativ, die kumulative Rezidivrate beträgt 20,3 % nach 13 Jahren (Kaplan-Meier). Säuresekretionsmessungen ergaben eine mittlere Reduktion der basalen (BAO) und mittleren stimulierten Sekretionswerte (MAO) von 80,7 bzw. 74,8 % ohne Unterschiede zwischen Patienten mit und ohne Rezidiv. Das Rezidivrisiko war für Ulcus duodeni (22 von 194) und pylorische Geschwüre (4 von 22) vergleichbar, ebenso fanden sich keine Unterschiede bezüglich dem Geschlecht, einer zusätzlichen Drainage-Operation, dem Rauchverhalten, akuter oder elektiver Operation und erstem oder Rezidivgeschwür. Nach der Operation komplizierter Ulzera war das Rezidivrisiko tendentiell höher (p 0,07). 78,5% der Patienten erreichten ein (sehr) gutes funktionelles Langzeitergebnis (Visick I oder II), nur 6% mußten als Visick III eingestuft werden. Die SPV kann daher als ein ungeachtet der Patienten-Compliance wirksames und wertvolles Therapieverfahren zur Behandlung des Ulcus duodeni erachtet werden.

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Results of highly selective vagotomy after 13 years

Summary This study reports the long-term results of 216 patients after highly selective vagotomy (HSV) for duodenal ulcers operated from 1970 through 1978 with a mean follow-up of 12.8 years (8.3–15). 26 patients developed symptomatic ulcer recurrences (12%) within 4 to 135 months following surgery, the cumulative recurrence rate (Kaplan-Meier) at 13 years was 20.3%. Acidity analyses showed a postoperative mean reduction of basal acid output (BAO) and maximal acid output (MAO) values of 80.7 % and 74.8 % respectively with no differences according to recurrences. The risk of recurrence was similar for duodenal (22/194) and pyloric ulcers (4/22) and no differences were found with respect to sex, additional drainage procedure, smoking habits, acute or elective operation and first or recurrent ulcers. Risk was slightly higher for complicated ulcers (p 0.07), but without reaching statistical significance. 78.5% of patients showed (very) good results (Visick I or II), only 6% were Visick III. HSV is therefore regarded as a valuable therapeutic measure for the treatment of duodenal ulcer independent of patient compliance.

     

Susceptibility contrast imaging of cerebral blood volume: human experience.

Magnetic resonance (MR) can offer a unique window on the structure/function relationships in the brain, by utilizing the established link between tissue function, metabolism, and hemodynamics. This report focuses on recent applications of MR-based cerebral blood volume (CBV) imaging in humans. Our methodology uses high-speed "single-shot" or echo planar imaging techniques, which provide the necessary temporal resolution for mapping the rapid cerebral transit of contrast agents. These MR CBV mapping techniques have been used to study normal human brain task activation and in the clinical study of patients with brain tumors. In the latter, positron emission tomography imaging was used for functional metabolic and CBV correlation. Susceptibility contrast CBV imaging should allow us to improve our understanding of the relationship between the detailed physiology and morphology of the microvascular bed and functional attributes of the brain. These techniques can be applied to understanding fundamental questions of cognitive neuroscience and can aid in improving diagnostic sensitivity and specificity in various neuropathologies.