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Biomedical subjects

D Grant

Publications and source records attributed to D Grant.

At least 253 records · Page 14Linked to original sources

Graft-versus-host disease associated with intestinal transplantation in the rat. Host immune function and general histology.

Graft-versus-host disease was studied on the 10th and 14th postoperative days in Lewis x Brown Norway F1 rats (LBN-F1) receiving Lewis accessory heterotopic intestinal allografts. LBN-F1 isograft recipients and LBN-F1 rats were used as controls. The rats were injected with sheep erythrocytes five days before sacrifice. Rats with graft-versus-host disease had progressive loss of the normal architecture of the lymphoid organs. Skin, liver, colon, and salivary glands were infiltrated with immunoblasts and had patchy areas of necrosis. Concurrent with these changes, there were significant, progressive reductions in hemolytic titers, splenocyte plaque-forming counts, viable splenocytes, and the in-vitro splenocyte response to stimulation with concanavalin A. Graft-versus-host disease following intestinal allotransplantation damages the host's lymphoid tissues, producing profound immunosuppression. This finding has implications for clinical intestinal transplantation.

Animals↗

Polycystic ovary syndrome in a virilised, premenarcheal girl.

A premenarcheal girl aged 12 years presented with an abdominopelvic mass and virilisation. A large ovarian cyst was removed at laparotomy. A histological diagnosis of polycystic ovarian syndrome was made, with no evidence of an associated masculinising tumour.

Child↗

Lung aeration and lung water dynamics in artificially ventilated newborn lambs.

To the present lung liquid dynamics in the immediate neonatal period have been measured mainly by gravimetric techniques. This paper explores lung aeration and lung water dynamics in seven fetal lambs between 139 and 142 days of gestation delivered by caesarean section and ventilated on a constant-volume respirator. After caesarean section and instrumentation, fetal lambs were quickly transferred to a warm X-ray table and connected to a volume-cycled respirator. X-ray fluoroscopic images of the chest commenced before the first breath and were recorded on video tape. After 1 h of ventilation, measurements were made of pulmonary blood volume, and lung samples were taken for wet weight and dry weight analysis. Fluoroscopic image brightness was calibrated by comparison with images obtained from a water wedge, which extended across the X-ray field. Thus image brightness was related to "equivalent water path length" through the thorax. Within a defined lung field, image brightness increases as the amount of lung water in the path of the X-ray beam is reduced. This occurs rapidly at first and then more slowly over the remaining hour. There was considerable variation between the reduction of liquid in the lung fields examined within the one animal, as well as the absolute amount of fluid that had been cleared during the 1st h.

Animals↗

Heparan sulfate proteoglycan is present in basement membrane as a double-tracked structure.

Basement membranes contain 4.5-nm wide sets of two parallel lines, along which short prongs called "spikes" occur at regular intervals. The nature of this structure, referred to as "double tracks," was investigated in Lowicryl sections of mouse kidney and rat Reichert's membrane immunolabeled for basement membrane components using secondary antibodies conjugated to 5-nm gold particles. When the mouse glomerular basement membrane and rat Reichert's membrane were exposed to antibodies directed to the core protein of heparan sulfate proteoglycan, 95% or more of the gold particles were over double tracks, whereas after exposure of Reichert's membrane to antisera against laminin, collagen IV, or entactin, labeling of the double tracks remained at the random level. When heparan sulfate proteoglycan was incubated in Tris buffer, pH 7.4, at 35 degrees C for 1 hr, a precipitate resulted which, on electron microscopic examination, was found to consist of 5- to 6-nm wide sets of two parallel lines along which densities were observed. Immunolabeling confirmed the presence of the proteoglycan's core protein in the sets. Since double tracks were closely similar to this structure and were labeled with the same antibodies, they were likely to be also composed of heparan sulfate proteoglycan.

Animals↗

Intestinal transplantation: current status.

Gut transplantation is at a stage comparable to that of transplantation of the heart and liver in the late 1960s. The feasibility of this procedure has been demonstrated in large animals but has not been successful in clinical practice. Rejection, sepsis, and possible GVHD are the major obstacles. Ongoing clinical trials can be justified on the basis of the limited options that are available for patients with the short gut syndrome who develop complications while on TPN, the improved results in animals studies, the recent clinical success of pancreaticoduodenal transplantation, and the demonstrated ability to detect rejection and remove the intestinal graft without mortality (Table 1).

Animals↗

Heparin binds to human monocytes and modulates their procoagulant activities and secretory phenotypes. Effects of histidine-rich glycoprotein.

The binding of heparin to human monocytes and the monocytoid cell line U937 was characterized. Heparin binding was rapid, specific, saturable, and reversible. There was a single class of heparin binding sites, with an apparent dissociation constant of 0.19 mumol/L and 1.9 x 10(6) sites per cell. The binding was not dependent on the anticoagulant property of heparin. Analysis of surface-iodinated cell lysates by heparin affinity chromatography revealed a major 120 Kd cell surface heparin-binding protein. Histidine-rich glycoprotein, a potent heparin antagonist found in human plasma and platelets, decreased the affinity of heparin for cell binding. Cell surface bound heparin was functionally active and markedly accelerated the inactivation of thrombin by antithrombin III. Heparin induced the release of two monocyte secretory proteins of 160 and 17 Kd. Our study supports the thesis that heparin and related glycosaminoglycans interact with monocytes and macrophages, as well as endothelial cells and smooth muscle cells, and play an important and complex role in blood vessel wall biology.

Binding Sites↗

Surgical management of spontaneous pneumothorax in patients with acquired immunodeficiency syndrome.

Spontaneous pneumothorax has been reported with increasing frequency in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia. In the past year, we treated 4 patients with spontaneous pneumothorax. All of them were treated with closed tube thoracostomy, and 1 patient with bilateral apical cysts eventually required bilateral thoracotomies and pleurectomies. Only 1 patient had an uncomplicated hospital course. The remaining patients had prolonged air leaks, and 2 had synchronous pneumothoraces. Pneumothorax appears to be associated with P. carinii pneumonia. We recommend closed tube thoracostomy as the initial treatment in symptomatic patients. Pleurectomy for air leaks persisting longer than seven days can be safely performed in patients fit for thoractomy.

Acquired Immunodeficiency Syndrome↗

Intensive care course following liver transplantation in children.

We report the postoperative intensive care course of 16 children who underwent 18 orthotopic liver transplantation (OLT) procedures in London, Ontario and compare this experience in our developing transplant center with that reported from the Children's Hospital of Pittsburgh. Assisted ventilation was required in all children, with six requiring ventilation for greater than three days. Six children required positive end expiratory pressure (PEEP) therapy and hypertension was common. Physiologic stability index score was initially high in all patients, but fell on subsequent days. Intensive care survival was 100% with 69% long-term survival, which compared favorably with the information from Pittsburgh. Septic complications, despite immunosuppressive therapy were rare, but hypocalcemia and hypomagnesemia were common.

Adolescent↗

Successful intestinal transplantation in pigs treated with cyclosporine.

To date, it has not been possible to reliably prevent intestinal allograft rejection in large animals. This study was undertaken to determine if continuous i.v. cyclosporine (CsA) followed by p.o. CsA would prevent rejection in outbred piglets with orthotopic, in-continuity intestinal allografts. Untreated recipients (n = 7) died of rejection (2), interstitial pnuemontitis (3), or technical complications (2) at 5.3 +/- 1 days. Intestinal recipients treated with i.v. CsA 8 mg/kg/day and i.v. steroids (n = 3) died of rejection (mean survival 11.3 +/- 3.2 days). CsA 20 mg/kg/day i.v. plus i.v. steroids for 21 days, followed by p.o. CsA 25 mg/kg/day (n = 6) prevented rejection; however, most of the recipients developed fatal infections (mean survival 28 +/- 8 days). Intravenous CsA 15 mg/kg/day for 7-10 days (n = 16), followed by p.o. CsA 30 mg/kg/day in tapering doses reliably prevented graft rejection, permitting long-term survival (mean survival 121 +/- 32 days). Rejection did not occur in 7 animals when CsA was discontinued at 97 +/- 11 days. Seven animals surviving more than 100 days maintained normal nutritional indices and gained weight at the same rate as control animals. This study provides a rationale for further experimentation to determine the feasibility of intestinal transplantation in man.

Actuarial Analysis↗