Transfusion-related acute lung injury secondary to biologically active mediators.

Transfusion-related acute lung injury is seen following the transfusion of blood components. The reported incidence is approximately 1 in 2000 transfusions. Clinically, it is similar to adult respiratory distress syndrome. The pathophysiology is unclear but has been attributed to HLA antibodies, granulocyte antibodies, and more recently to biologically active mediators in stored blood components. We report a case with laboratory evidence that supports the role of biologically active mediators in the pathogenesis of transfusion-related acute lung injury. To our knowledge, the case reported here is the first to use lipid extractions of patient samples to determine that lipid-priming activity was present at the time transfusion-related acute lung injury was identified clinically.

Centralization of histocompatibility laboratories: impact on organ allocation efficiency and outcomes of cadaveric renal transplantation.

This project was undertaken to determine whether centralization of histocompatibility laboratory services for renal transplants performed within eastern Pennsylvania could improve the efficiency of allograft allocation and short-term allograft function. A nonconcurrent cohort study was performed comparing renal allografts transplanted between September 15, 1993, and September 14, 1994, to those transplanted between September 15, 1994, and September 14, 1995. All allografts were procured and allocated by the Delaware Valley Transplant Program, the organ procurement agency in eastern Pennsylvania. Cold preservation time and delayed allograft function were used to measure efficiency of allograft allocation and short term allograft function, respectively. The mean cold preservation time was reduced from 25.08 hours to 20.68 hours (P < 0.001). The percentage of delayed allograft function was 19.9 and 17.4 for the pre- and postcentralization groups, respectively (P = 0.5). Therefore, centralization of histocompatibility tissue typing was a regionally effective process intervention for reducing cold preservation time without adversely impacting short-term graft function. The magnitude of this reduction varied between individual centers. Further investigation is required to determine the effect on long-term allograft function and system wide costs.

Do histocompatibility antigens influence the risk of head and neck carcinoma?

Associations were sought between specific histocompatibility antigens (HLA) of the human major histocompatibility complex and the incidence of head and neck squamous cell carcinoma (SqCC). Seventy sequential patients with SqCC and 217 control subjects from the same geographic region were typed for HLA-A, HLA-B, and HLA-DR loci. These results were compared. Multivariate statistical analysis using stepwise logistic regression revealed significant associations between the incidence of SqCC and HLA-B14, HLA-DR3, and HLA-DR4 as well as smoking and the sex-smoking interaction. The authors concluded that certain host factors, including genetic constitution, and behavioral characteristics (i.e., smoking) as well as tumor biology, can influence the development of SqCC. The mechanism(s) of these associations may involve as yet undefined relationships between HLA region genes and the immune response.

HLA antigens influence resistance to lung carcinoma.

The concept of genetic factors playing a role in the pathogenesis of lung cancer has gained increased attention. The present study was undertaken to reexamine the question of HLA antigen association with carcinoma of the lung. In a study of 90 patients, a significant association occurred between HLA-DR7 and resistance to lung cancer, after accounting for smoking status and sex. HLA class I antigens were also implicated. These results suggest that major histocompatibility complex loci affect carcinoma of the lung.

Prostaglandin production in chronic progressive multiple sclerosis.

Peripheral blood monocytes have been implicated in the immune reactions that accompany demyelination in patients with multiple sclerosis (MS). We measured prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) release from peripheral monocytes exposed in vitro to complement. Our studies suggest that there is a significantly higher production of PGE2 in monocytes from patients with chronic progressive MS than in those with exacerbation or remitting MS and healthy controls. No significant differences in TxB2 release were noted between the three groups.

Immunologic monitoring studies in advanced cancer patients treated with recombinant human gamma interferon (IFN-gamma 4A).

Thirty-nine patients with a variety of advanced malignancies were treated with recombinant IFN-gamma 4A (AMGen, specific activity 1 to 5 x 10(7) U/mg protein). IFN-gamma 4A was administered at a dose of 10-2,000 micrograms/m2/d. Following a 2-week rest, a maintenance phase was continued with injections 3 d/wk. Immunologic monitoring studies were performed on patients' peripheral blood cells before administration of IFN-gamma 4A, then on Days 15 and 90. Flow cytometric analysis was used to determine the absolute number of CD 3+, CD 4+, CD 8+, CD 19+, and CD 16+ cells using a panel of monoclonal antibodies. Natural killer (NK) cell function was assayed by monitoring lysis of the K562 cell line in the Cr51 release assay. Changes from baseline were observed on Days 15 and 90 in all parameters studied, although the ratio of helper to suppressor cells seemed to remain within the normal range. Whereas there were no substantial changes in CD 3+ and CD 4+ cells on Day 15, IFN-gamma 4A had an enhancing effect on CD 8+, CD 19+, and CD 16+ cells. This trend continued at Day 90 only for CD 19+ and CD 16+ cells at the higher dose levels. An increase in functional NK cell activity at Day 15 was less noted on Day 90. Comparison of intravenous (IV) to intramuscular-subcutaneous (IM-SC) administration showed differences in the effect on lymphocyte subpopulations at 450 and 1,000 micrograms. The effect of IFN-gamma 4A on the equilibrium among lymphocyte subpopulations and the possibility of its role in combination therapy with other biologic response modifiers are discussed.

A phase I trial of recombinant human gamma interferon (IFN-gamma 4A) in patients with advanced malignancy.

We report a Phase I study in 39 cancer patients of the tolerance and biologic activity of 47 intravenous (i.v.), intramuscular (i.m.), and subcutaneous (s.c.) treatments with recombinant methional gamma interferon (IFN-gamma 4A) which most closely resembles the natural material produced by T lymphocytes. Patients were treated with IFN-gamma 4A 5 days a week for 2 weeks. After a 2-week rest period, patients were placed on the same dose of drug three times a week. The most common side effects--fever, chills, malaise, myalgias, and nausea and vomiting--were seen with all routes of administration. Reversible increases in hepatic transaminase and decrease in granulocytes counts were seen. The dose-limiting toxicities observed were malaise and orthostatic hypotension. The maximum tolerated dose was 500-1,000 micrograms/M2/day. The t1/2 of IFN-gamma 4A in the circulation was 20 min after i.v. injection. No blood levels were detected after i.m. or s.c. injection. Antibody against IFN-gamma 4A increased in three patients. A complete response was observed in one patient with pulmonary metastases from renal cell carcinoma.

Duodenal acidification inhibits sphincter of Oddi motility in the prairie dog.

Recent studies have explored the influence of various hormones, peptides, and neural innervation on the sphincter of Oddi (SO). However, only older and conflicting data are available on the effect of intraduodenal (ID) perfusion of acid on SO activity. Therefore, we tested the hypothesis that acidification of the proximal small bowel would alter SO motility. In acute terminal experiments, 19 adult male prairie dogs underwent cannulation of the gallbladder (GB) with a pressure-monitored perfusion catheter. The common bile duct was cannulated proximally with a drainage catheter and distally with a triple-lumen, side-hole, closed-tip catheter with one port positioned in the SO. The duodenum was cannulated distal to the SO to allow perfusion of the proximal 30 cm of intestine with saline. SO phasic wave frequency (F), amplitude (A), and baseline pressure as well as GB pressure were measured for 40 min prior to and during ID perfusion of saline at pH 8.8, pH 6.0, or pH 2.0. A SO motility index (MI = F X A) was calculated for each 10-min period of the experiment. Infusion of saline at pH 8.8 had no effect on SO function. ID perfusion of saline at pH 6.0 reduced SO MI to 39% (P less than 0.05) and 34% (P less than 0.05) of control values at 20-30 and 30-40 min, respectively. ID saline at pH 2.0 reduced the SO MI to 51% (P less than 0.01) and 53% of control values during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid hormone levels in heart and kidney cadaver donors.

Experimental animal work has shown that thyroid hormone levels become undetectable 9 hours after brain death. It is unknown whether such an acutely hypothyroid state contributes to the hemodynamic instability of brain-dead donors or whether these donors should be resuscitated with thyroid hormone. No previous clinical study has examined thyroid hormone levels in human brain-dead organ donors. We retrospectively examined the thyroid hormone levels as measured by triiodothyronine and thyroxine in 22 human cadaver donors. Eight donors provided heart and kidney allografts, and the remaining 12 were kidney donors only. No donor had a normal triiodothyronine level and 10 were below normal, with undetectable levels in 12. Thyroxine levels were normal in 10 and below normal in 12. In comparing donors with below normal to undetectable triiodothyronine levels and donors with normal to below normal thyroxine levels, no statistically significant differences were found regarding blood pressure during harvest, duration of harvest, or dopamine requirements during harvest. Donors with a closed-head injury plus multiple injuries had statistically lower thyroxine values than donors with only a closed-head injury. For the heart donors, no correlation was found between thyroid hormone levels and the duration or dose of dopamine required for the heart allograft recipients after transplant. The incidence of acute tubular necrosis in the kidney transplants did not correlate with the donor thyroid hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

A phase II study of Catrix-S in solid tumors.

Catrix-S is an acidic mucopolysaccharide complex derived from bovine tracheal cartilage. This material was administered by weekly subcutaneous injection (5.0-7.5 g/week) to nine patients with progressive metastatic malignancy. One complete response was seen in a patient with metastatic renal cell carcinoma to the lungs. Eight patients had progression of their disease. No undue toxicity and no consistent immunologic alteration was noted.

Early events in the formation of a venous thrombus following local trauma and stasis.

A jugular vein was exposed in 20 cats divided into four groups of five cats each. In group 1 the vein was removed immediately after exposure. In group 2 the vein was removed after three 5-minute periods of stasis and reflow. Groups 3 and 4 had the jugular vein occluded for 24 and 72 hours, respectively. In all groups, veins were perfused under physiologic pressure by heparinized saline to remove blood and immersed in 2.5% glutaraldehyde for fixation. All vessels were prepared for scanning and transmission electron microscopy. Group 1 cats had a normal-appearing luminal surface. Group 2 cats had deposition of leukocytes with few erythrocytes or platelets. Groups 3 and 4 had deposition of leukocytes, platelets, and erythrocytes. Leukocytes were found in all areas and associated with all cell types. Platelets and erythrocytes were seldom found in the absence of leukocytes. Thrombi were found on normal-appearing and damaged endothelium. The majority of thrombi were found at side branches and valve pockets. Our results suggest that leukocytes play a primary role in the initiation of deep vein thrombosis. Platelets may have only a secondary role.

Specific MLC stimulation by cultured B cells.

Pairs of cultured T and B lymphoid cells, derived from the same individual, were used as stimulating cells in MLC experiments. Blastogenic response to cultured B cells were much greater than those to the corresponding T cell line. These cells will provide a useful reagent for isolation and characterization of B cell specific antigens.