Psychosocial intervention with the child cancer patient and family

Malignancy in the child or adolescent presents a major life stress for all concerned—patient, family, and professionals. All too often, psychological impairment results in the patient and family members. Adequate psychosocial intervention must take into consideration the influence of the patient's age on his or her understanding of illness and death, the characteristic reactions of parents and siblings, and the key points in the course of the illness.     

The concept of the disability process.

The accident process, by which excessive stress, tension, and denied dependency needs are transformed by an accident or illness into an “acceptable” disability is described, along with a graphic summary of the disability process. Suggestions are given for preventing or minimizing such disability states.     

Transfer of contact sensitivity to beryllium using dialyzable leukocyte extracts (transfer factor).

Transfer factor derived from lymphocytes of donors with strong cellular immunity against beryllium was intradermally or subcutaneously injected into unprimed or subclinically primed human recipients who were patch test-negative. These recipients were challenged with beryllium at weekly intervals thereafter. Subjects who had been subclinically primed and received transfer factor either intradermally or subcutaneously showed transient patch test reactivity to the challenge. Subjects who received transfer factor but were not primed and subjects who had been primed but did not receive transfer factor showed no such conversion. This is the first demonstration of transfer of contact sensitivity in man using transfer factor, and it suggests that subclinical priming is necessary for such transfers.     

Activation of promutagens by liver homogenates isolated from female mice at different ages; lack of significant differences

Liver S-9 (9000 g supernatant) fractions isolated from 2-, 12- and 26-month untreated female Swiss-Webster mice were compared under different assay conditions as to their abilities to activate 2-acetylaminofluorene, benzo(a)pyrene, and dimethylnitrosamine to mutagens in Salmonella typhimurium tester strain TA 100. All fractions activated these compounds to mutagens, although 2-acetylaminofluorene was only weakly mutagenic. Some differences in the activating abilities of the three age groups were observed but they were for the most part relatively small.     

Radioenzymatic assay for measurement of tissue concentrations of histamine: adaptation to correct for adherence of histamine to mechanical homogenizers

Because adherence of histamine to glass is well-known, we tested for its adherence to a mechanical homogenizer commonly used in the extraction of histamine from tissue samples. During 60 sec of homogenization, 15% to 17% of the histamine originally present in the samples "disappeared," and the reason for the disappearance was reversible binding of histamine to the homogenizer. Adding trace amounts of [14C]histamine to each sample before homogenization and measuring the disappearance of radioactivity during homogenization permitted correction for binding to the homogenizer. This technique for correction was validated by the measurement of endogenous concentrations of histamine in the tracheal posterior membranes of six dogs (range of mean concentrations: 0.63 to 1.51 ng/mg wet weight) followed by the measurement of known amounts of exogenous histamine added before homogenization to tracheal tissue samples from the same dogs. In the latter samples, 96 +/- 13% (mean +/- SEM) of the histamine added was measured by our technique. We conclude that binding of histamine to mechanical homogenizers may be an important cause of inaccuracy of the enzymatic assay for the measurement of histamine concentrations in tissue but that such binding may but that such binding may be easily corrected for.     

Ocular allergy and immunology.

The eye may be the target of allergic inflammation in a large number of systemic immunologic conditions. Ocular signs and symptoms can often be the most striking and disabling aspects of such diseases. The eye is also affected by several local conditions in which immunologic mechanisms are thought to play a significant role. Certain anatomic and physiologic features appear to endow the eye with a unique immunologic reactivity which has made this organ of special interest to allergists and immunologists.     

Induction of persistent tolerance to urushiol in humans

Young nonimmune subjects were injected intramuscularly multiple times with small amounts of urushiol oil derived from poison oak. One week after the last injection this group and another group of age-matched controls were exposed to a sensitizing dose of the oil painted on the skin. All were challenged at 1 mo, then each year for 7 yr. Initially all experimental subjects were tolerant to high challenge doses; this persisted for 1 yr, at which time experimental subjects were no longer completely tolerant but were clinically tolerant (hyporeactive). This state persisted for at least 4 yr, and this represents complete tolerance followed by long-lasting hyposensitization.     

Life events, risk factors, and coronary disease.

Are high levels of stress from life events correlated with increased levels of smoking, blood pressure, and cholesterol? The authors used a life events questionnaire to determine the level of presumptive stress in a sample of 575 middle-aged men who were initially selected for inclusion in the larger, collaborative Multiple Risk Factor Intervention Trial (MRFIT). Significant differences in stress levels were found only between smokers and nonsmokers. Therefore, the authors suggest that smoking behavior be included as a variable in studies of the relationship between psychological stress and illness.     

Psychiatric Liaison Support Groups For General Hospital Staffs

The value of psychiatric liaison services to hospital staffs is exemplified by liaison support groups. Including medical, nursing, and ancillary personnel, these groups strive to reduce work-related stress, which, left unchecked, can lead to depression, work dissatisfaction, and a high rate of personnel turnover. The group structure is designed to encourage the staff to ventilate their concerns, receive constructive feedback, bolster morale, and improvepatient care. The author enumerates the problems support groups encounter, particularly resistance, and describes how they function by providing examples and comparisons with group psychotherapy.     

In Vitro translation of rabies virus messenger RNAs

RNA isolated from rabies virus-infected cells directed the in vitro synthesis of the five major rabies virus structural proteins.     

Migraine

Instead of representing two sharply different entities, migraine and tension headache may best be thought of as occupying the two ends of a continuum, with mixed tension and vascular headache in the center. The author's assessment of current knowledge of mechanisms, symptoms, and acute and prophylactic treatments supports his statement that the major clinical difference between the variants of headache is differential pharmacologic effectiveness of the drugs used.     

Blood Coagulation Factor Fibrinogen in Tumor Pathogenesis of Central Nervous System B-Cell Lymphoma

Central nervous system (CNS) lymphoma is an extranodal non-Hodgkin B-cell lymphoma characterized by malignant lymph tissue arising in the brain or spinal cord, associated with inflammation and blood-brain barrier (BBB) disruption. Although BBB disruption is known to occur in patients with CNS lymphoma, a direct link between these two has not been shown. Herein, abundant deposition of the blood coagulation protein fibrinogen around B-cell lymphoma was detected in CNS lymphoma patients and in the CNS parenchyma in an orthotopic mouse model. Functional enrichment analysis of unbiased cerebrospinal fluid proteomics of CNS B-cell lymphoma patients showed that coagulation protein networks were highly connected with tumor-associated biological signaling pathways. In vivo two-photon imaging demonstrated that lymphoma growth was associated with BBB disruption, and in vitro experiments identified a role for fibrinogen in promoting lymphoma cell adhesion. Overall, these results identify perivascular lymphoma clustering at sites of fibrinogen deposition, and suggest that fibrinogen may be a target for pharmacologic intervention in metastatic B-cell lymphoma associated with BBB disruption.

Central nervous system (CNS) lymphoma is a form of non-Hodgkin B-cell neoplasm that can occur as either a primary or a metastatic disease.1, 2, 3 Both primary and metastatic CNS lymphomas show accumulation of tumor cells around blood vessels, implicating the cerebrovasculature in their pathogenesis.² Dissemination of lymphoma cells within the CNS is associated with poor prognosis. During CNS tumor development, the blood-brain barrier (BBB) can be damaged as a primary or a secondary event.^4,5 Loss of integrity in the BBB closely correlates with how fast individual metastases grow,⁶ and meta-analyses indicate a significant association between BBB leakage and degree of malignancy.^7,8 However, the relationship between BBB leakage and CNS lymphoma onset or progression has not been demonstrated.BBB disruption allows plasma protein extravasation and deposition in the brain parenchyma. Indeed, a large-scale proteomic profiling of the cerebrospinal fluid (CSF) of patients with CNS lymphoma identified increased levels of coagulation factors, including fibrinogen,⁹ which correlated with tumor grade and poor clinical outcome.¹⁰ Interestingly, activation of the coagulation cascade seems to be crucial for tumor growth and metastasis-associated events.¹¹ In addition, apart from its role in coagulation, fibrinogen has been shown to drive tissue inflammation during CNS injury and disease.¹² However, whether fibrinogen is deposited in CNS tumors in lymphoma patients and its potential role in lymphoma accumulation in CNS tumors have not been investigated.This study makes use of human tumor samples and a mouse model of CNS lymphoma to investigate whether CSF protein extravasation through a permeable BBB can alter the tumor microenvironment to regulate the CNS tropism behavior and adhesion properties of CNS tumors. The results demonstrate that fibrinogen deposition occurs in the CNS parenchyma of an orthotopic mouse model of human B-cell lymphoma and in primary CNS lymphoma patients. Unbiased proteomic profiling of CSF from patients with metastatic B-cell CNS lymphoma revealed a molecular link between coagulation and signaling related to CNS lymphoma growth and progression. Lymphoma cells adhered to fibrinogen in vitro, and two-photon imaging of lymphoma in the brain showed that lymphoma tends to cluster around sites of BBB disruption. These data show, for the first time, the cellular and molecular interplay of fibrinogen and lymphoma growth signaling pathways, and can provide tumor-specific targets for pharmacologic intervention in lymphoma associated with BBB disruption.