Activation of human macrophages. Comparison of other cytokines with interferon-gamma.

Cytokines affecting mononuclear phagocytes were screened for activation of human macrophages to secrete H2O2 and kill toxoplasmas. In contrast to recombinant interferon-gamma (rIFN gamma), the following factors, tested in partially or highly purified form and over a wide range of concentrations, did not augment these functions: native interferon-alpha (nIFN alpha), rIFN alpha A, rIFN alpha D, rIFN beta, colony stimulating factor (type 1) (CSF-1), CSF for granulocytes and macrophages (GM-CSF), pluripotent CSF (p-CSF), tumor necrosis factor (TNF), native interleukin 2 (nIL-2), and rIL-2. Partially purified migration inhibitory factor (MIF) enhanced H2O2-releasing capacity submaximally without inducing antitoxoplasma activity, and warrants further study.

Occurrence of hepatitis A, B, and non-A/non-B in the United States. CDC sentinel county hepatitis study I.

To determine the relative occurrence of hepatitis A, B, and non-A/non-B in the United States, serum samples and epidemiologic data were collected from patients with hepatitis in five selected counties. Overall, 41, 33, and 26 percent of the patients had hepatitis A, hepatitis B, and hepatitis non-A/non-B, respectively. The incidence, especially of hepatitis A, varied considerably. All three types of hepatitis occurred more frequently in those 15 to 44 years of age. Hepatitis A predominated in those less than 15 years of age and non-A/non-B predominated in those older than 44 years. There was a male predominance (65 to 62 percent) for hepatitis A and hepatitis B, but non-A/non-B occurred equally in both sexes. There was no seasonal pattern for any type. Risk factors for hepatitis A were previous contact with a patient with hepatitis (26 percent), homosexual (male) preference (15 percent), and day-care center contact (11 percent). For hepatitis B, risk factors included drug use (26 percent), previous contact with an infected person (22 percent), homosexual preference (12 percent), and a health-care occupation (12 percent). For hepatitis non-A/non-B, risk factors included drug use (16 percent), transfusion (12 percent), and previous contact with an infected person (12 percent). Previous hospitalization appeared to be a risk factor for both hepatitis B and hepatitis non-A/non-B.

Futility and the common cold. How requests for antibiotics can illuminate care at the end of life.

The dominant approach to futility in medicine assumes that the probability and utility of medical interventions may be separated to provide a quantitative (probabilistic) definition of futility. This assumption is not only misleading but also responsible for much of the confusion that futility has engendered in medical discussions. The divorce of utility from probability is the opposite of how clinicians reason: an improbable intervention looks different if it is cheap, easy, and without morbidity than if it is technology intensive, expensive, and likely to involve great pain and suffering. Futility is how physicians describe the sense of being compelled to proceed with resource intensive care for marginal benefits. Outside the intensive care unit, physicians weigh and sometimes reject patient requests without the need to invoke futility. By examining the ways that physicians can legitimately evaluate patient requests, we can show that appeals to futility are both unnecessary and counterproductive. In cases where such appeals are unavoidable, the outpatient model suggests a process to adjudicate the competing claims of patient autonomy and physician responsibility.

Medical abortion complications. An epidemiologic study at a mid-Missouri clinic.

PIP: A study of 420 cases of vacuum aspiration abortions in a central Missouri family planning clinic found 33 postabortal complications, 14 of which occurred over 10 weeks; 12 under 7. Most patients were white nulliparous females under 30. 41.5% of complications were incomplete abortions, only one of which occurred between 7 1/2-9 1/2 weeks, 4 times more at less than 7 weeks, 11 times more for women over 10 weeks. 25% were cervical lacerations, which occurred less frequently at advanced stages of gestation, 21.2% were postabortal hemorrhage, occurring most frequently over 10 weeks. The optimum time for less risk of postabortal complications is 7 1/2-9 1/2 weeks gestation. 18% complications, 7% incomplete abortions occurred at 7 1/2-9 1/2 weeks. During early pregnancy the progesterone block influences uterine motility and may be a survival mechanism for the fetus. The corpus luteum of pregnancy secretes large amounts of progesterone for the first 60 days and lesser quantities for the next 30 days.^ieng

Advance care planning: pitfalls, progress, promise.

We now have a decade of experience with advance directives since the Patient Self-Determination Act was signed into law in November 1990. With few exceptions, empirical studies have yielded disappointing results. Advance directives are recorded by medical personnel more often but are not completed by patients more frequently. The process of recording them does not enhance patient-physician communication. When available, advance directives do not change care or reduce hospital resources. The most ambitious study of advance care planning, the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments, failed to show any change in outcomes after an extensive intervention. Investigators have attempted to identify the reasons why the optimism about the Patient Self-Determination Act has not been realized. Many interventions to facilitate advance care planning were focused on specific treatment decisions. Recent research suggests that preferences for care are not fixed but emerge in a clinical context from a process of discussion and feedback within the network of the patient's most important relationships. Clinical trials emphasizing this approach have been successful. The approach that emphasizes communication, building trust over time, and working within the patient's most important relationships offers a hopeful model for clinicians working in intensive care units.

Resolving conflicts surrounding end-of-life care.

Critical care physicians are frequently called on to negotiate issues of medical management with patients, their families, and other physicians. These decisions frequently revolve around end-of-life care. Recent data suggest that such discussions are manageable. In one study, 57% of patients and surrogates agreed immediately to a physician's recommendation to limit intensive care and 90% agreed within 5 days, while multiple treating physicians came to consensus about such limits within 4 days in 92% of cases. If conflicts are rare, they are strongly felt. They arise when any one of the parties to a decision insists on continued care against the considered judgment of another. Since the alternative to aggressive ICU care is usually the death of the patient, it seems difficult to reconcile a physician's refusal to treat with patient autonomy. The concept of a fiduciary offers a model of the physician-patient relationship in which the physician commits himself to the patient's best interests but retains a role in defining those interests. This model offers significant benefits over medical futility in negotiating conflicts over end-of-life care.

Withholding or withdrawal of life-sustaining therapy.

Seventy percent of deaths in intensive care units are preceded by decisions to limit life-support, most of which are made in consultation with the patient's family or other surrogates. Even when the outcome is clear, surrogates and physicians may deny that death is imminent and delay removing ventilatory assistance and other supportive measures. To avoid prolonging suffering, end-of-life decisions should always be guided by the interests and wishes of the patient.

Increasing incidence of withholding and withdrawal of life support from the critically ill.

To determine whether limits to life-sustaining care are becoming more common, we attempted to quantify the incidence of recommendations to withhold or withdraw life support from critically ill patients, to describe how patients respond to these recommendations, and to examine how conflicts over these recommendations are resolved. In 1992 and 1993 we prospectively enrolled 179 consecutive patients from two intensive care units (ICUs) for whom a recommendation was made to withhold or withdraw life support. Where possible, we compared results with data collected in the same units over a similar time period in 1987 and 1988. Recommendations to withhold or withdraw life support preceded 179 of 200 deaths (90%) in 1992 and 1993, compared with 114 of 224 deaths (51%) in 1987 and 1988 (chi2 = 73.76, p < 0.001]. Cardiopulmonary resuscitation was initiated in 10% of deaths in 1992 and 1993 as compared with 49% in 1987 and 1988. Ninety percent of patients agreed within less than 5 d, and only eight patients (4%) refused physicians' recommendations to limit life support. In cases of conflict, physicians in 1992 and 1993 deferred to patients with one exception: physicians were willing to refuse surrogate requests for resuscitation of patients they considered hopelessly ill. We conclude that 90% of patients who die in these ICUs now do so following a decision to limit therapy, that this represents a major change in practice in these institutions over a period of 5 yr, that most patients and surrogates accept an appropriate recommendation to withhold or withdraw life support, and that physicians will refuse surrogate requests in certain circumstances.

A national survey of end-of-life care for critically ill patients.

In some intensive care units (ICUs), fewer patients who die now undergo attempts at cardiopulmonary resuscitation (CPR), and many more have life support actively withdrawn prior to death than did a decade ago. To determine the frequency of withdrawal of life support, we contacted every American postgraduate training program with significant clinical exposure to critical care medicine, asking them prospectively to classify patients who died into one of five mutually exclusive categories. We received data from 131 ICUs at 110 institutions in 38 states. There were 6,303 deaths, of which 393 patients were brain dead. Of the remaining 5,910 patients who died, 1,544 (23%) received full ICU care including failed cardiopulmonary resuscitation (CPR); 1,430 (22%) received full ICU care without CPR; 797 (10%) had life support withheld; and 2,139 (38%) had life support withdrawn. There was wide variation in practice among ICUs, with ranges of 4 to 79%, 0 to 83%, 0 to 67%, and 0 to 79% in these four categories, respectively. Variation was not related to ICU type, hospital type, number of admissions, or ICU mortality. We conclude that limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs. There is wide variation in end-of-life care, and efforts are needed to understand practice patterns and to establish standards of care for patients dying in ICUs.

A retrovirus vector expressing the putative mammary oncogene int-1 causes partial transformation of a mammary epithelial cell line.

In mammary tumors induced by the mouse mammary tumor virus (MMTV), the int-1 gene is frequently activated by adjacent proviral insertions and is thereby strongly implicated in tumorigenesis. To seek a direct biological effect of int-1 that would validate its proposed role as an oncogene, we constructed a retrovirus vector containing the gene and examined its effects on tissue culture cells. Expression of int-1 in a mammary epithelial cell line caused striking morphological changes, unrestricted growth at high cell density, and focus formation on a monolayer, although the cells were not tumorigenic in vivo. This partial transformation induced by int-1 was not observed in cells infected by an otherwise identical virus bearing a frameshift mutation in the gene. These findings strongly support the hypothesis that int-1 plays a functional role in MMTV-induced mammary tumorigenesis.

Seizures after eating a snack food contaminated with the pesticide endrin. The tale of the toxic taquitos.

In September 1988 we investigated reports of seizures in persons who had eaten taquitos, a commercially prepared snack food. We identified and interviewed 5 persons with new-onset seizures within 12 hours of eating taquitos, all purchased during a 1-week period from a single store. Leftover taquitos were found to contain endrin, a highly toxic chlorinated hydrocarbon pesticide. Although tissue confirmation of exposure to endrin was not possible and the level of contamination in the tested taquitos was below that previously thought to be capable of inducing seizures, the pattern of symptoms and the common time and place of purchase strongly suggested that the seizures were due to endrin-contaminated taquitos. The source of endrin contamination could not be determined. This episode is the first report of illness associated with endrin-contaminated food products in the United States.

Pleural paragonimiasis in a Southeast Asia refugee.

We report a Laotian patient with pleural paragonimiasis who did not have the usual diagnostic triad for this parasitic disease. He did not have chronic hemoptysis (considered by many to be an "invariable" finding), there were no pulmonary infiltrations, and stool and sputum examinations did not yield Paragonimus ova. The diagnosis was made on the basis of ova found in the pleural fluid. Paragonimiasis pleural effusion did not resolve with bithionol, the drug of choice for pulmonary paragonimiasis, and, as a result, chest tube drainage was required. The difference between pleural paragonimiasis and pulmonary paragonimiasis is that the classic clinical presentation of the latter (hemoptysis, ova in sputum and stools, lung infiltration, etc.) requires an intrapulmonary location on the parasite. A search for ova in the pleural fluid may be the only diagnostic tool for patients suspected of pleural paragonimiasis. With the influx of Southeast Asia refugees, this case report may be of relevance to U.S. physicians involved in the care of patients in whom not all chronic pleuropulmonary diseases are tuberculous.