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Biomedical subjects

D B Paul

Publications and source records attributed to D B Paul.

At least 19 recordsLinked to original sources
PubMed2001

Immunologic approaches to therapy for brain tumors.

Malignant brain tumors are notoriously invasive. Although surgical debulking can relieve the patient of the main mass of tumor, adjuvant treatments are needed to target the glioma cells that infiltrate through normal parenchyma as single cells or pockets of tumor cells from which recurrent tumors arise. Successful adjuvant cellular therapy of brain tumors, or activation of endogenous immune cells, requires that either cell effectors make direct contact with tumor cells or come within close proximity to them and exert an indirect effect. This review examines current clinical trials aimed at direct lysis of glioma cells and trials making gliomas more visible to the endogenous immune system.

Animals↗
PubMed2000

The human leukemic T-cell line, TALL-104, is cytotoxic to human malignant brain tumors and traffics through brain tissue: implications for local adoptive immunotherapy.

Preclinical studies with the human MHC nonrestricted cytotoxic T-cell leukemic line, TALL-104, were performed in anticipation of its use in cellular immunotherapy trials for primary malignant brain tumors. In this study, we have: (a) quantitated the in vitro brain tumor cell lysis; (b) measured the cytokine secretion upon coincubation of TALL-104 cells with brain tumor cells; (c) investigated the effect of dexamethasone on brain tumor cell cytolysis by TALL-104 cells; (d) explored the effects of lethal irradiation and cryopreservation on TALL-104 cell viability and lytic efficacy; and (e) estimated the damage TALL-104 cells induce to murine normal and tumor brain cells and their trafficking patterns in both normal and tumor-bearing rat brain upon intracranial infusion. In vitro coincubation of TALL-104 cells with human brain tumor cells, explants, and cell lines resulted in significant lysis of them, but normal brain cells were spared. Lysis of tumor at 4 h was unaffected by dexamethasone or lethal irradiation. Secretion of tumor necrosis factor-alpha, tumor necrosis factor-beta, IFN-gamma, or granulocyte/macrophage-colony stimulating factor upon TALL-104 cell coincubation with brain tumor cells variably occurred without always correlating with lysis. In vivo experiments using irradiated TALL-104 cells, placed at multiple times into normal cannulated rat brain, produced focal sterile abscesses at the instillation site but no widespread allergic encephalitic reaction. Cells morphologically consistent with TALL-104 cells specifically trafficked from the site of instillation through the neuropil, occasionally into the contralateral brain, and egressed at perivascular and leptomeningeal spaces. In vivo experiments with cannulated rats bearing 9L gliosarcoma showed a preferential localization of the TALL-104 cells in tumor compared with normal brain. Taken together, these data support the concept that TALL-104 cells can be used as a novel nontoxic and efficacious paradigm for cellular immunotherapy trials in human primary malignant brain tumors.

Animals↗
PubMed2000

B7.1 expression by the weakly immunogenic F98 rat glioma does not enhance immunogenicity.

Enhanced immunogenicity has been reported following transfection of a variety of immunogenic tumors with the B7.1 co-stimulatory molecule. The purpose of the present study was to determine if transfection of a weakly immunogenic rat brain tumor, the F98 glioma, with the gene encoding B7.1 could enhance its immunogenicity. F98 cells were transfected with a plasmid containing the B7.1 gene, and stable transfectants (F98/B7.1) were obtained. Flow cytometric analysis confirmed the expression of B7.1 and MHC class I antigens on the cell surface. To investigate the effects of B7.1 expression on the tumorigenicity of the F98 glioma, Fischer rats were implanted intracerebrally with either F98 (wild-type) or F98/B7.1 transfected cells. No significant differences in survival times were noted. Mean survival times of 21.8 and 24.0 days were observed for the respective groups at a challenge dose of 103 cells. These differences in survival time were not significant. To determine if expression of B7.1 enhanced the immunogenicity of the F98 glioma, rats were vaccinated weekly for 3 weeks with 107 mitomycin C-treated F98 or F98/B7.1 cells injected subcutaneously and then challenged intracerebrally with F98 cells 1 week later. Unvaccinated animals or those that received wild-type F98 cells as a vaccine had a survival time (mean +/- s.d.) of 22.3 +/- 1.5 days following tumor challenge versus 20.0 +/- 1.7 days for rats that had been vaccinated with F98/B7.1. Although we recognize that it might be possible to design more effective vaccination regimes, nevertheless, our data indicate that transfection of the B7.1 gene into the F98 rat glioma did not enhance its immunogenicity, and that other approaches will be required.

Animals↗
PubMed1999

What is a genetic test, and why does it matter?

How the term 'genetic test' is defined, matters for social policy. The past few years have witnessed many efforts to enact legal barriers specifically against genetic discrimination. To the extent that information derived from genetic tests receives special protection, both enthusiasts for genetic medicine and those who stress its perils have an incentive to adopt a broad interpretation of genetic testing. However, the consequences have not always been those anticipated.

Confidentiality↗
PubMed1999

Traditional criteria for observation of splenic trauma should be challenged.

Age less than 55 years, normal Glasgow Coma Score (GCS), and absence of hypotension are traditional criteria for the selection of adult patients with blunt splenic trauma for observation. The objective of this study is to challenge these criteria. Two hundred twelve patients who presented with blunt splenic injury between 1992 and 1997 were identified from the Trauma Registry at our Level I trauma center. The patients were divided into three groups: 100 patients (47%) were observed, 108 (51%) underwent immediate splenorrhaphy or splenectomy, and 4 (2%) failed observation. The three groups were compared by participants' ages, GCSs, and histories of hypotension. No statistical differences were noted between the successfully observed patients and those requiring immediate surgery with respect to these criteria. Of the 4 patients who failed observation, all were younger than 55 years, all had a GCS >12, and all were normotensive. Our findings suggest that traditional criteria used to select patients for splenic trauma observation are not absolute indicators and should be liberalized: patients can be successfully observed despite having criteria that, in the past, would have led to immediate operative intervention.

Blood Pressure↗
PubMed1996

Early tracheostomy in trauma patients.

A retrospective analysis of 118 trauma patients who underwent tracheostomy for airway and pulmonary management was undertaken. Timing of the procedure was defined as early (0-3 days), intermediate (4-7 days), and late (> 7 days). Head injury patients received tracheostomy early (p < 0.00003). Aspiration evaluated by modified bedside aspiration test was a frequent occurrence in all three groups with no difference in incidence (p < 0.34). Pneumonia was less frequent in the early group compared with the intermediate and late groups (p < 0.0034). The incidence of pneumonia in the early group was not different from that observed in early extubated patients (n = 282; p < 0.23). Our study suggests that early tracheostomy may decrease pulmonary septic complications in trauma patients. Although no change in length of stay can be attributed to the early performance of tracheostomy, preventing pneumonia in the intensive care unit setting with its resulting high expense is beneficial.

Adult↗
PubMed1995

The hidden science of eugenics.

The early eugenicists were not stupid, but they did not share our social values. The rise and fall of the eugenics movement is a history that modern medical geneticists would do well to heed.

Animals↗
PubMed1995

Short-term stability of HIV provirus levels in the peripheral blood of HIV-infected individuals.

Changes in viral load have been reported to reflect disease progression or response to therapy; however, the stability of HIV DNA levels in HIV-infected individuals has not been extensively studied. Cellular HIV DNA levels in infected individuals were evaluated over a short time period to determine degree of variability as well as any correlation with other measurements of virus load or immune status. Peripheral blood mononuclear cells (PBMC) were obtained several times over 1 month from 32 asymptomatic or symptomatic non-AIDS, HIV-infected individuals currently on AZT therapy. PCR amplification of the HIV gag region was performed with DNA from PBMC lysates and the PCR amplified products quantitated by liquid phase hybridization. HIV DNA levels in the majority of the patients were relatively stable, with 26 of 32 persons having less than threefold change. Changes over the study period were both positive and negative, and the median change in HIV DNA levels was 68.6%. These changes were found to positively correlate with fluctuations in plasma p24 levels. In contrast, no correlations were found with other measurements of immune system activity, including changes in CD4 number, CD4 percent, and beta 2-microglobulin when compared with provirus changes. This study shows that levels of HIV DNA can be relatively stable over short periods in most non-AIDS, HIV-infected persons.

Base Sequence↗
PubMed1994

Blunt vascular injury associated with closed mid-shaft femur fracture: a plea for concern.

During a period of six years, 765 consecutive patients were treated by the trauma service at Allegheny General Hospital for closed mid-shaft femur fractures that were a component of their injury complex. Thirty-one patients underwent angiography of the involved extremity for indications including loss of pulses in eleven and large hematomas or deformities of the thigh in the remainder. Ten patients (1.3%) were found to have acute vascular injuries. In nine patients there was an intimal flap of the superficial femoral artery (SFA), and in one, a pseudoaneurysm. Two patients had injuries of the femoral nerve. Three patients had no other associated major injuries (Injury Severity Score range, 10-19). Twelve months after the initial injury, one patient developed an arteriovenous fistula of the SFA. Detailed, repeated physical examinations, early utilization of angiography, and intensive follow-up by the trauma surgeon or orthopedic surgeon of patients with closed mid-shaft femur fractures should lead to early recognition of this potentially serious association.

Adolescent↗
PubMed1994

Enhanced rim around infarcted, traumatized spleen on computed tomographic scans: case report.

Computed tomography is considered a reliable imaging technique when determining the extent of splenic injury. We present the case of a patient with a traumatic infarct of the spleen detected by computed tomographic scanning of the abdomen. During laparotomy there was an infarction of the spleen from a hilar injury in addition to bleeding from the splenic vein. We conclude that ongoing bleeding from the splenic hilar vessel can lead to a rim of enhancement around the spleen from contrast material. This should be taken into account when a decision is made for nonsurgical management.

Abdominal Injuries↗
PubMed1994

Diving injuries: a preventable catastrophe.

During a 5-year period from January 1987 through January 1992, 58 patients were admitted to the Allegheny General Hospital trauma center for non-scuba, non-suicidal diving injuries. There were 46 men and 12 women (mean age, 23 years). Forty-five patients were injured in swimming pools. Twenty-two patients had blood alcohol levels > 100 mg/dL. Cervical spine injury was the most common pathologic entity encountered in this group of patients. Closed head injury, pelvic fracture, thoracic vertebral fracture, and rib fractures were other injuries identified. Some patients had multiple organ failure syndrome. Aquatic recreational activities carry a risk for injury that is preventable. The mechanism, clinical data, and complications of 58 patients are presented and the importance of prevention is discussed.

Adolescent↗
PubMed1994

Delayed rupture of the spleen--myths, facts, and their importance: case reports and literature review.

Over a 1-year period, three patients were seen in our trauma service with delayed bleeding (> or = 7 days) from an initially inapparent splenic injury. This entity was defined as a late occurrence of signs and symptoms attributed to splenic injury not detected by diagnostic computed tomographic (CT) scanning during the initial examination. We believe that this represents an "injury in evolution" minor enough to go undetected on initial CT scans of the abdomen. A high index of suspicion and liberal utilization of imaging techniques are essential for the identification of delayed splenic rupture. Further multicenter studies are required to delineate the true incidence of its occurrence and its clinical significance. We conclude that "delayed rupture" of the spleen is a true clinical entity. The occurrence of a delayed rupture may prove hazardous to patients discharged early from the hospital after blunt abdominal injury. A classification system to assess this type of injury is suggested.

Accidents, Traffic↗