Humanistic qualities in end-of-life care: lessons from the diving bell and the butterfly: a memoir of life in death-required reading in an end-of-life care curriculum for internal medicine residents.

OBJECTIVE: Reading a literary account of a terminal illness to develop humanistic qualities and attitudes for effective end-of-life care. METHOD: The Diving Bell and the Butterfly: A Memoir of Life in Death by Jean-Dominique Bauby is an autobiographical account of Mr. Bauby's experiences in the locked-in state after he suffered a brain stem stroke at age 43. Each resident was given a copy of this paperback to read over 4 weeks. Interns (PGY-1) were on a 4-week oncology ward rotation, and all junior and senior residents (PGY-2 and PGY-3) were on elective rotations during this period. Residents were instructed to mark their favorite passages of the book, to be prepared to read aloud such passages in small-group sessions, and to explain why they chose the specific passage. Attendance was mandatory, and residents were asked to complete a questionnaire at the end of the small-group discussion. RESULTS: Eighteen PGY-ls and 30 PGY-2/3s completed the curriculum. Seventeen of 18 PGY-ls read the entire book, and all 30 PGY-2/3s read the book from cover to cover. Only 3 of 18 PGY-1 residents felt that the task of reading this book interfered with their work. More than 90% of the residents felt that reading the book clearly improved their attitudes toward the care of the terminally ill patient. Lessons learned from the book included all the humanistic qualities important in caring for the terminally ill and severely disabled. CONCLUSION: Well-chosen narratives of literature can be a powerful tool to learn attitudes and humanistic qualities in the care of the terminally ill.

Primary breast cancer in aberrant breast tissue in the axilla.

Primary breast cancer in aberrant axillary breast tissue is rare. Breast cancer in the axilla is most often due to lymph node metastases from an ipsilateral breast tumor or from an occult primary lesion. We describe two patients with primary breast cancer in aberrant breast tissue in the axilla, and review the literature to define guidelines for diagnosis and treatment.

Long-term subcutaneous infusion of midazolam for refractory delirium in terminal breast cancer.

We describe the case of a 56-year-old woman with terminal metastatic breast cancer who had delirium in the form of frightening hallucinations, paranoid delusions, and nightmares resulting in violent agitation. During this period, her bone pains from metastases were well controlled with narcotic analgesics, but her delirium proved refractory to standard doses of drugs such as lorazepam, diazepam, and haloperidol. We report the use of a subcutaneous infusion of midazolam at home and its effectiveness in control of her delirium after other drugs had failed.

Primary pulmonary non-Hodgkin's lymphoma.

A 48-year-old woman with an asymptomatic lung mass on a routine chest roentgenogram was found to have a primary non-Hodgkin's lymphoma involving the lung. Extensive evaluation revealed no evidence of lymphoma at any other site. She required an open lung biopsy for definitive diagnosis and was found to have unresectable tumor at thoracotomy. The patient achieved a complete remission with combination chemotherapy and remains in clinical remission 14 months after completion of therapy.

Spontaneous regression of acquired immune deficiency syndrome-related, high-grade, extranodal non-Hodgkin's lymphoma.

Spontaneous regression of low-grade non-Hodgkin's lymphoma often has been reported. Proposed mechanisms of this event have included concomitant infections and enhanced cellular and humoral antitumor responses by the host. Spontaneous regression of high-grade non-Hodgkin's lymphoma is rare and has never been reported in a patient with acquired immune deficiency syndrome (AIDS). The authors report a patient with spontaneous regression of AIDS-related non-Hodgkin's lymphoma and discuss the role of host immunity in mediating spontaneous regression.

Pernicious anemia. Early identification to prevent permanent sequelae.

Pernicious anemia can be confidently diagnosed in a patient who has megaloblastic hematopoiesis, low serum cobalamin level, and impaired vitamin B12 absorption correctable by administering intrinsic factor. Recent studies suggest that neurologic disorders in patients with pernicious anemia are less severe than in the past, highly responsive to therapy, and seen in the absence of anemia and macrocytosis. A low serum cobalamin level in the absence of anemia, particularly in a patient with a neurologic disorder, should not be ignored.

Effect of nisoldipine on priming and activation of the human neutrophil respiratory burst.

Nisoldipine inhibits calcium (Ca++) influx in human neutrophils: Preincubation with the dihydropyridine, nisoldipine (1.5 microM) resulted in a 30% decrease in [45]Ca++ influx during formyl-methionine-leucine-phenylalanine (FMLP) stimulation in primed as well as resting cells. Although the drug does not inhibit Ca++ dependent effector functions elicited by FMLP, e.g. superoxide (O2-) production, it inhibits FMLP priming, a phenomenon that is independent of extracellular Ca++. Nisoldipine exhibited a narrow dose response with an ED50 of ca. 1 microM and total inhibition of primed O2- response at 1.5 microM. Nisoldipine (1.5 microM) also abolished the incremental rise of Ca++i in primed neutrophils stimulated with FMLP. The dissociation of nisoldipine inhibitory effects on cell effector function and Ca++ transport were corroborated in studies with neutrophils stimulated with influenza virus and phorbol myristate acetate (PMA), stimuli which do not exhibit an extracellular Ca(++)-dependence in their elicited responses. Unlike in FMLP-stimulated cells, nisoldipine reduced influenza virus and PMA initiated respiratory burst, indicating that this drug has inhibitory effects on neutrophil function independent of its effect on Ca++ metabolism. Possible sites of action are postulated at phospholipase A2 or calmodulin-regulated activities. Caution is thus required in interpreting the effects of dihydropyridine on cell function, when the drug is used at micromolar concentration.

Influenza A virus and the neutrophil: a model of natural immunity.

Natural immune reactions are mediated by lymphocytes, macrophages/monocytes, and neutrophils. The latter have been implicated in a variety of self-surveillance models, i.e., activity against malignant host cells, participation in wound repair, and infliction of damage in postischemic perfusion injury. Better characterized are the interactions with unopsonized pathogens through lectinophagocytosis mechanisms, where the lectin resides either on the phagocyte or on the microorganism. This review examines the infection by influenza A virus (IAV) of the human neutrophil, which results in the vigorous metabolic response of the cell to generate toxic oxygen species. This response is not necessarily characteristic of response to unopsonized particles, as the neutrophil exhibits no such activity to unopsonized zymosan or chlamydia. The virus elicits calcium mobilization from intracellular stores through a pertussis toxin-insensitive mechanism, and in its particulars the activation cascade is unique in comparison to any other characterized agonist. The putative receptor for the IAV binding protein, hemagglutinin (HA), contains the sialic acid residues; identification of specifically linked protein receptors will allow characterization of this stimulation pathway and will define the molecular biology of this activation sequence. Insight into this particular pathway may allow definition of a primitive recognition system that represents a fundamental basis for discernment of self and nonself entities.

Nonsecretory multiple myeloma in a 26-year-old man with acquired immunodeficiency syndrome, presenting with multiple extramedullary plasmacytomas and osteolytic bone disease.

High grade B-cell lymphoma and leukemia have been well described in patients with the acquired immunodeficiency syndrome (AIDS). Malignant transformation of more differentiated lymphoid cells has not been well described in these patients. We report a 26-year-old man with AIDS-associated multiple myeloma, who had a highly unusual presentation and clinical course. A review of the literature indicates that monoclonal gammopathy in patients seropositive for the human immunodeficiency virus (HIV) is common. Multiple myeloma and extramedullary plasmacytomas, diseases that are extraordinarily rare in young persons, are now being reported in patients with AIDS and should be added to the list of neoplastic diseases now associated with HIV infection.

Priming of human neutrophils with N-formyl-methionyl-leucyl-phenylalanine by a calcium-independent, pertussis toxin-insensitive pathway.

Resting neutrophils may be "primed" to augmented effector function, eg, superoxide (O2-) production in the respiratory burst, upon a second stimulation with a variety of soluble agonists including formylated methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA). At priming concentrations of FMLP (5 x 10(-9) mol/L) that did not initiate O2- generation, two metabolic activities were noted: (1) approximately a threefold increase in the baseline intracellular calcium (Ca++i) level, that was not dependent on extracellular Ca++, and (2) a rapid rise in intracellular pH that was blocked by 5-(N,N-dimethyl) amiloride (DA), that had no effect on the Ca++i response to priming. Furthermore, there were no significant increases in inositol metabolites in cells primed and stimulated with FMLP compared with cells receiving the stimulating dose of FMLP alone and pretreatment with pertussis toxin (PT) (before the addition of the priming -5 x 10(-9) mol/L dose of FMLP), whereas abolishing the response to FMLP during the second stage of stimulation, had (1) no effect on FMLP-primed cells subsequently stimulated with PMA, and (2) only partially ablated the rise in Ca++i initiated with FMLP. That FMLP priming involved distinctive processes to those of the well characterized FMLP-coupled Ca++-dependent activation cascade was shown by the full priming effect attained in a Ca++-free buffer, which did not sustain an O2- response to a second-stage FMLP stimulation, but sustained a primed response to PMA. These data demonstrate that FMLP primes human neutrophils by a Ca++-independent and PT-insensitive pathway, offering a functional model for studying heterogeneous FMLP receptor-coupled reactions.