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Biomedical subjects

L Norton

Publications and source records attributed to L Norton.

At least 19 recordsLinked to original sources

Depression of cell-mediated immunity in diabetes.

Parameters of cell-mediated and humoral-mediated immunity were measured in ten infection-free, insulin-dependent, controlled diabetic patients and in ten similar but nondiabetic patients awaiting elective operations. Tests performed included total and differential leukocyte counts, neutrophil reduction of nitroblue tetrazolium, mitogen response of lymphocyte to phytohemagglutinin, ratio of thymus-derived to bone marrow-derived lymphocytes, serum immunoglobulins IgA, IgG, and IgM, macrophage inhibition factor, serum zinc, and reaction to skin test antigens. Diabetics had a significantly (P less than .05) decreased mean response response to phytoheagglutinin stimulation and a lowered ratio of thymus-derived to bone marrow-derived lymphocytes. These findings support the concept of depressed cell-mediated immunity in the controlled, adult diabetic and might explain the propensity of the uncontrolled diabetic to increased frequency and severity of bacterial infection.

Adult

Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs.

Methotrexate (MTX) followed by citrovorum factor (CVF) rescue was evaluated for its effectiveness in reducing graft-versus-host disease (GVHD) in lethally irradiated dogs transplanted with bone marrow from unrelated histoincompatible donors. Animals were given no immunosuppressive therapy (group A) or a combined regimen of MTX and CVF (group AMC). These two groups were compared with a group of animals transplanted earlier given MTX alone (group AM). Ainmals in the AMC group lived significantly longer than the A group (p less than 0.05). Engraftment rate, hematopoietic recovery and incidence of GVHD were similar in all three groups. Incidence of early deaths was significant in the AM group (p less than 0.05). It is concluded that MTX combined with CVF increases survival and is an effective posttransplantation immunosuppressive regimen with minimal toxicity.

Animals

The continuing challenge of duodenal injuries.

Thirty-four cases of duodenal trauma, 23 caused by gunshot wounds, are reviewed. All but three patients had associated major organ injuries, a total of 97 injuries. Postoperative mortality was 14% for injuries into the duodenal lumen. Techniques for operative repair included simple primary closure, use of omental or serosal patches, controlled fistula with a duodenostomy tube, decompressive and feeding ostomies, "diverticulization", segmental duodenal resection and anastomosis, and total duodenectomy and pancreatectomy. It is emphasized that the surgeon finding duodenal injury must be familiar with all of these techniques, each of which has its indications. Treatment of duodenal injuries perhaps more than any other bowel trauma must be individualized.

Adult

Accuracy of techniques to detect intraperitoneal abscess.

Three new diagnostic techniques, gray-scale ultrasonography, gallium-67 scanning (67Ga), and computed tomography (CT) were used in combination to detect intraperitoneal abscess in 30 patients. All 30 had sonography, 24 were scanned for 67Ga, and 15 underwent CT. Nine had three tests and 21 had two. Accuracy of results was evaluated by subsequent laparotomy in 16 and by clinical impression in the remainder. Ultrasound was accurate (true positive and true negative) in 12 of 16 (75%) operated patients, with 12% false-positive and 12% false-negative results. Gallium correctly diagnosed nine of 14 (64%) operated patients having 22% false-positive and 14% false-negative diagnoses. CT was accurate in five of seven (71%) patients evaluated by operation, with 14% false positives and 14% false negatives. Overall accuracies for both operated and clinical groups was ultrasound 57%, gallium 54%, and CT 67%, not significantly different results. Three tests agreed in only two of nine patients (22%), with no single test more accurate than another. Two tests agreed in 57%, with no test superior to another. It is concluded that ultrasonography, 67Ga scanning, and CT each have significant limits in diagnosing intra-abdominal pus. No single test is better than another. Disagreement among test results in the same patient obviates use of more than one technique in most instances.

Abscess

Lack of therapeutic synergism between vincristine and methotrexate in L1210 murine leukemia in vivo.

In vivo studies were performed in mice bearing L1210 ascites tumor to examine the interaction of vincristine (VCR) at doses of 0.15 and 1.5 mg/kg with methotrexate (MTX) at doses of 0.5, 5, 50, and 350 mg/kg. The combination was administered on Days 2, 6, and 10 after tumor inoculation. VCR was given either concurrently with MTX or preceding it by 30, 60, or 120 minutes. VCR administered at a dose of 0.15 mg/kg achieved a peak peritoneal fluid concentration of 1.4 micron declining with a half-life (T1/2) of 33.5 minutes and produced no in vivo augmentation of MTX uptake. VCR administered at a dose of 1.5 mg/kg achieved a peak peritoneal fluid concentration of 16.5 micron declining with a T1/2 of 24.9 minutes and produced significant in vivo augmentation of MTX uptake when given concurrently with the MTX and 30 minutes prior to MTX at a dose of 350 mg/kg. No other interval was associated with augmented MTX uptake. When animal survival was evaluated, no therapeutic synergism was observed at any dose level of either drug in any schedule. In fact, VCR (0.15 and 1.5 mg/kg) and MTX at doses of greater than or equal to 50 mg/kg produced toxic synergism which adversely affected survival. Since the drug doses studied are comparable with those used in "high-dose" clinical protocols, individual tumor evaluation is indicated to support the use of these drugs in combination.

Animals

Growth curve of an experimental solid tumor following radiotherapy.

Because it has long been recognized that the growth of most untreated tumors is well described by Gompertzian or exponential growth curves but that the growth of treated tumors has never been well characterized mathematically, we developed and applied an equation that, while not dependent on restrictive assumptions or unmeasurable variables, was nevertheless capable of describing perturbed as well as unperturbed growth. For the 3964A rat hepatoma, a functional relationship between dose level of radiotherapy and growth-curve response was derived and used for predictive purposes. An implied relationship between tumor size and sensitivity to therapy and some clinical implications were examined.

Animals

Migration of transfused granulocytes in leukopenic dogs.

Although granulocyte transfusion therapy has been shown to be effective in infected granulocytopenic animals and humans, the relative effectiveness of granulocytes (PMN) harvested by continuous flow centrifugation (CFC) or by continuous flow filtration leukapheresis (FL) remains uncertain. Studies in vitro of morphology and granulocyte functions have suggested cells collected by FL may be damaged. To compare the function in vivo of granulocytes collected by different methods, dogs were made granulocytopenic with cyclophosphamide (CYT) and then transfused with granulocytes collected by CFC or FL. The local neutrophil mobilization (LNM) through a standard skin abrasion into a chamber containing a strong chemoattractant, autologous serum, was measured. Greater LNM was found after transfusions of CFC PMN than after transfusions of the same number of FL PMN (p less than 0.0003). This difference persisted even when the dose of FL PMNs was four times greater than that of CFC mn and when the FL donor was pretreated with steroids (p less than 0.001). These results suggest that during filtration leukapheresis, granulocytes are functionally altered and that their function in vivo may be compromised.

Animals

Multiple organ failure.

Forty-two postoperative patients, each with demonstrable failure of two or more vital organ systems, have been studied as they define a syndrome of multiple organ failure. They typify the emerging clinical entity of patients kept alive solely by reason of specific mechanical and pharmacologic support. Trauma initiated hospitalization in 40 per cent and major bleeding, in 11 per cent. Sepsis was judged to be of etiologic significance in 69 per cent. Complications in clinical management were, in retrospect, thought to be of contributory etiologic significance in 57 per cent. Twenty-nine of 42 patients died; a mortality of 69 per cent. Mean duration of multiple organ failure was 30.5 days. Hospital cost, omitting the physician's fees, was conservatively estimated at $700 per day. Scientific, social, moral, ethical and legal factors emphasize the need to establish a statistically valid large data base concerning this new man-made syndrome which has both important scientific and social implications. This study is a first step in this direction.

Abdomen, Acute

Hepatic support with hepatocyte suspensions in a permeable membrane dialyzer.

Hepatic support by whole liver, liver slice, or hepatocyte perfusion is unsatisfactory. A new concept of support with circulating hepatocytes on one side of a cuprophan membrane and blood from an anhepatic pig on the other was evaluated in 19 dialysis experiments. Levels of pyruvate metabolism and oxygen utilization were similar to those obtained when liver cells in a centrifuge are perfused with oxygenated plasma. Of six anhepatic pigs given late hepatic support, five showed neurologic improvement. One had concomitant improvement in electroencephalographic results. A membrane hemodiolysis unit in which hepatocytes circulate against blood from an anhepatic animal is the most suitable extracorporeal liver support unit described so far. Its simplicity allows repeated and prolonged use.

Animals

Community experience with small bowel bypass for morbid obesity.

A comparison of small bowel bypass performed at university centers and by private practitioners in a large metropolitan area demonstrates definite stmilarities in terms of patient selection, mortality and morbidity, and weight loss results. The only aspect of small bowel bypass in the private sector that could be criticized would be the adequacy of follow-up. An operation with as many known and probably other unknown long-term complications as jejunoileal bypass necessitates prolonged careful patient follow-up. We belive the person most qualified to provide such follow-up is the surgeon who performed by bypass procedure.

Adolescent

Hepatocyte perfusion within a centrifuge.

A centrifuge, as used in blood banks for washing erythrocytes, is shown to be a good perfusion chamber for hepatocyte suspensions being evaluated for potential extracorporeal liver support. The perfusate was cell-free oxygenated--pO2 300 millimeters of mercury--plasma, serum or tissue culture medium. A centrifuge that requires intermittent perfusion cannot deliver sufficient oxygen to maintain prolonged viability. A continuous flow unit can, at a flow of 800 milliliters per minute, support most functions of 100 grams of hepatocytes for six hours and some function for 12 hours. Metabolism of 2-14C tagged pyruvate to 14CO2 is the most useful sensitive measurement of liver function in this system. It is concluded that a centrifuge allowing a constant perfusion of oxygenated plasma into hepatocytes kept within the unit by centrifugal force is a suitable base for extracorporeal liver support.

Animals