Gene therapy and blood cell transplantation.

OBJECTIVES: To describe the basics of gene transfer and specific applications in marrow ablative therapy. DATA SOURCES: Review articles, research studies, and book chapters pertaining to gene therapy. CONCLUSIONS: Gene therapy will be a major factor in healthcare options for the 21st century. Genetically engineered biopharmaceuticals will probably have a place in the blood cell transplant regimens of the future. IMPLICATIONS FOR NURSING PRACTICE: Nurses are in a position to guide the successful implementation of gene therapy through their roles as patient educator, counselor, direct-care coordinator, consultant, and through development of resource materials.

Biology of lung cancer.

OBJECTIVES: To provide a review of the biology of lung tumor development and progression, and advances in gene and antimetastatic therapies. DATA SOURCES: Review articles, research studies, and book chapters pertaining to the biology of lung cancer. CONCLUSION: Advances in understanding the molecular basis of lung cancer initiation, promotion, and progression will provide more effective methods of early detection and treatment of this disease. Promising new treatment methods based on tumor biology include gene therapies, antibodies against growth factors, and agents that prevent angiogenesis and tissue invasion. IMPLICATIONS FOR NURSING PRACTICE: An understanding of the biology of cancer assists nurses with the development of protocols for the assessment and monitoring of patients receiving treatments based on cancer biology. Oncology nurses will assume important counseling roles with the development of genetic testing and prognostic markers.

Neuroendocrine and immunological responses of women to stress.

Natural killer (NK) cell activity, cortisol and catecholamine levels, and physiological reactivity were examined in 15 healthy women who volunteered to take a cognitive stress test (the Stroop test). Relationships were explored among the physiological and selected psychosocial variables. Urine and blood samples were taken to examine catecholamine and cortisol concentrations and NK cell activity immediately before, immediately after, and hourly for 6 hours after the Stroop test. During the Stroop test, heart rate, skin conductance, peripheral skin temperature, and blood pressure were measured. Although skin conductance, heart rate, and blood pressure increased in response to the Stroop test, neuroendocrine values did not. Cortisol secretion decreased after the Stroop test and appeared to follow the normal circadian rhythm. NK cell activity was variable among individual participants but tended to increase over time.

Pattern of occurrence and clinical presentation of neurological complications in bone marrow transplant patients.

Neurological complications in bone marrow transplant (BMT) patients include central nervous system (CNS) infection, seizure, cerebrovascular accidents, and CNS disease recurrence. The purpose of this study was to describe the pattern and distribution of CNS complications and responses during BMT and to describe the presentation and outcome of select neurological incidents. The records of 200 BMT patients undergoing transplantation in 1989 were randomly selected and comprise the sampling unit for this study. Generally, the peak occurrence of CNS complications was pretransplant through day 21 posttranplant. Neuropathy and somnolence occurred earliest, peaking on day -13 and -8 pretransplant, respectively; confusion or disorientation peaked around day 12 posttransplant. Fifteen patients (7.5%) experienced seizure or suspected seizure, principally of the tonic-clonic type. Fifty-two patients (26%) experienced coma or encephalopathy. Etiologies included respiratory compromise, renal failure, and hepatic dysfunction, often occurring simultaneously. Coma and encephalopathy were commonly associated with terminal events. Because nurses are often the first to identify sensory and perceptual alterations in BMT patients, these results may assist nurses in the early detection of CNS complications.

The effects of hydrogen peroxide rinses on the normal oral mucosa.

Oral mucosal effects of hydrogen peroxide mouth rinses were investigated in normal volunteers. Following a 2-week control period, 35 subjects were randomly assigned to rinse with either normal saline, 1/4-strength hydrogen peroxide (0.75%), or 1/2-strength hydrogen peroxide (1.5%), 4 times daily for 2 weeks. Mucosal status, buccal microbial adherence, salivary flow rate (SFR), and subjective reactions were assessed weekly. In the normal saline group, no significant changes were noted in any of the observed parameters and subjective reports were unremarkable. In both hydrogen peroxide groups, significant mucosal abnormalities were observed (p < 0.001) and subjective complaints were numerous. Bacterial adherence was significantly reduced in the 1/4 hydrogen peroxide group but not in the 1/2 hydrogen peroxide group. Despite reports of dry mouth, SFRs were not altered significantly. Since hydrogen peroxide rinses are associated with mucosal abnormalities and elicit overwhelmingly negative subjective reactions in normal individuals, they are not recommended for oral care.

Adverse reproductive outcomes and occupational exposures among nurses: an investigation of multiple hazardous exposures.

1. The increasing numbers of pregnant women and women of childbearing age who are employed and exposed to hazardous substances pose occupational health concerns. 2. The findings of this study indicate the importance of not minimizing concern about exposure to radiation. Radiation monitoring should be implemented to a greater extent, and methods to measure low dose chronic radiation exposure should be developed. 3. Synergy between the adverse reproductive effects from multiple workplace factors among nurses, including but not limited to radiation, video display terminal use, and chemotherapeutic agents, warrants further evaluation.

Perspectives on human response to health and illness.

Nursing's domain has been defined as the diagnosis and treatment of human responses to health problems, yet debate rages over what "human responses" are. Without clear meanings for this and other terms used in nursing, the profession cannot claim that its practice is scientifically based, nor can it share that base among disciplines.

Suppression of basal plasma cortisol and adrenal androgen concentrations, but not of ACTH and cortisol responses to hCRH by low-dose dexamethasone in rhesus monkeys.

Glucocorticoid treatment at replacement doses does not result in a suppression of ACTH and cortisol responses to corticotropin-releasing hormone (CRH), while basal plasma concentrations of cortisol and adrenal androgens are efficiently suppressed 34 h after starting treatment. This finding could be demonstrated in rhesus monkeys receiving a continuous infusion of dexamethasone (1 microgram/kg per h) for 48 h and confirms our observations in patients on alternate-day prednisone therapy and in patients with congenital adrenal hyperplasia on glucocorticoid replacement therapy. We conclude that the decrease of basal adrenal steroid secretion resulting from glucocorticoid replacement therapy represents an effect on hypothalamic rather than on pituitary function.

Direct ultrastructural evidence of target-directed polarization by cytotoxic lymphocytes in lesions of human graft-vs-host disease.

Cytotoxic lymphocytes are thought to kill target cells by means of potent cytotoxic granules that congregate near the microtubular organizing center and the Golgi apparatus at one pole of the killer cell. We searched for evidence of this type of polarization in 12 lip biopsy specimens from patients with acute and/or chronic graft-vs-host disease (GVHD) compared with two lip specimens from normal individuals. Lymphocytes with such polarization were found in contact with epithelial cells of the squamous mucosa in all 12 cases of GVHD, and cells of the cuboidal minor salivary duct epithelium were found in two of 11 evaluable cases. The data add support to the hypothesis that cytolytic lymphocytes attack epithelial cells in GVHD.

Young rete ridge keratinocytes are preferred targets in cutaneous graft-versus-host disease.

Recent data show that stem cells in primate epidermis are concentrated at the bases of rete ridges. Because the early lesions of graft-versus-host disease (GVHD) in the vertebrate skin are in basal epidermis and hair follicle cells, the authors hypothesized that stem cells or their early progeny might be targeted. In this study they used morphometric methods to examine the distribution of the lesions of GVHD in the skin and lip of human bone marrow allograft recipients. They found that rete ridges are the primary sites of attack in early GVHD of the skin. They also found that the concentration of stem cells in ridges for various anatomic sites (body or arm, palm or sole, and lip) is directly proportional to the frequency and concentration of the lesions of GVHD. Osmotic fragility and the expression of early differentiation antigens related to the major histocompatibility complex are discussed as potential explanations for this phenomenon.

The fine structure of human rectal epithelium in acute graft-versus-host disease.

We compared the fine structure of the biopsied rectal mucosa of seven allogeneic bone marrow transplant recipients who had gastrointestinal graft-versus-host disease (GVHD) with that of four recipients without GVHD. In GVHD, lymphocytes formed the predominant cellular infiltrate. Lymphocytes indented the cytoplasmic membranes of enterocytes by point contact, extended broad pseudopods to the nuclear membranes of the enterocytes, and surrounded desmosomes. The membranes of target cells were never breached, however. We hypothesize that these lymphocyte-to-epithelial-cell contacts represent the recognition phase of alloimmune T-lymphocyte cytolysis. Damage to the enterocytes resulted in both coagulative necrosis and "apoptosis" (the development of membrane-bound cell fragments--"apoptotic bodies"). Epithelial injury and lymphocytic infiltration predominated in the bases of the crypts in mild GVHD and extended to the surface epithelium in severe GVHD. Chemoradiotherapy-induced injury, present early post-transplant, was diffuse and severe but transient. In GVHD, damage to the enterocytes, necrosis, and intercellular edema extended beyond the time of resolution of chemoradiotherapy-induced injuries. Patients without GVHD, studied after resolution of chemoradiation injury, had rectal epithelium with little or no injury and no evidence of either increased numbers of lymphocytes or of the intimate lymphocyte-to-epithelial-cell contacts described in those with GVHD.

The ultrastructure of the human epidermis in chronic graft-versus-host disease.

The epidermal ultrastructure of 11 allogeneic bone marrow recipients with chronic graft-versus-host disease (GVHD) was compared with that of 4 recipients without chronic GVHD. This electron microscope study revealed three patterns of epidermal injury typical of chronic GVHD. The first type was a nonacantholytic (nondissecting) injury with a prominent cellular infiltrate consisting primarily of lymphocytes accompanied by a few macrophages. The second type was an acantholytic (dissecting) injury with a prominent infiltrate, while the third was a nondissecting injury with a sparse infiltrate. Broad-zone contact was observed between lymphocytes and all epidermal cell types as well as between other lymphocytes and macrophages. Point contact was only observed between lymphocytes and epidermal cells. Lymphocytes appeared to detach desmosomes from adjacent keratinocytes by isolating them with cytoplasmic projections, a phenomenon not previously described. Typical damage to the epidermal cells in the basal and spinous layers consisted of either swelling of the organelles or condensation of the cytoplasm and nucleus. In the keratinocyte, the condensation reaction resulted in the formation of colloid bodies, some of which were phagocytized by macrophages. Besides the cytolytic events, a concurrent stimulatory reaction occurred in the epidermal cells. The number of melanosomes in melanocytes and of Langerhans cell granules and dense bodies in the Langerhans cells all increased. Extensive areas of replication and disruption of the basal lamina were subjacent to areas of necrosis in the basal layer.

Chronic cutaneous graft-versus-host disease in man.

This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed.